NM_001366722.1(GRIP1):c.10_13del (p.Val4fs) AND Fraser syndrome 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 28, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002510453.1

Allele description [Variation Report for NM_001366722.1(GRIP1):c.10_13del (p.Val4fs)]

NM_001366722.1(GRIP1):c.10_13del (p.Val4fs)

Gene:

GRIP1:glutamate receptor interacting protein 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12q14.3

Genomic location:

Preferred name:

NM_001366722.1(GRIP1):c.10_13del (p.Val4fs)

HGVS:

NC_000012.12:g.66678894_66678897del
NG_021400.2:g.395371_395374del
NM_001178074.2:c.10_13del
NM_001366722.1:c.10_13delMANE SELECT
NM_001366723.1:c.134-81968_134-81965del
NM_001366724.1:c.134-81968_134-81965del
NM_001379345.1:c.134-81968_134-81965del
NM_001379346.1:c.10_13del
NM_001379347.1:c.134-81968_134-81965del
NM_001379348.1:c.134-81968_134-81965del
NM_001379349.1:c.59-81968_59-81965del
NM_001379351.1:c.59-81968_59-81965del
NM_021150.4:c.10_13del
NP_001171545.1:p.Val4fs
NP_001353651.1:p.Val4fs
NP_001366275.1:p.Val4fs
NP_066973.2:p.Val4fs
NC_000012.11:g.67072674_67072677del
NM_021150.3:c.10_13delGTCT

Protein change:

V4fs

Molecular consequence:

NM_001178074.2:c.10_13del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001366722.1:c.10_13del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001379346.1:c.10_13del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_021150.4:c.10_13del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001366723.1:c.134-81968_134-81965del - intron variant - [Sequence Ontology: SO:0001627]
NM_001366724.1:c.134-81968_134-81965del - intron variant - [Sequence Ontology: SO:0001627]
NM_001379345.1:c.134-81968_134-81965del - intron variant - [Sequence Ontology: SO:0001627]
NM_001379347.1:c.134-81968_134-81965del - intron variant - [Sequence Ontology: SO:0001627]
NM_001379348.1:c.134-81968_134-81965del - intron variant - [Sequence Ontology: SO:0001627]
NM_001379349.1:c.59-81968_59-81965del - intron variant - [Sequence Ontology: SO:0001627]
NM_001379351.1:c.59-81968_59-81965del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Fraser syndrome 1 (FRASRS1)
Synonyms:: Cryptophthalmos with other malformations
Identifiers:: MONDO: MONDO:0054737; MedGen: C4551480; Orphanet: 2052; OMIM: 219000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002819876	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Dec 28, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002819876

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Dec 28, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002819876.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: GRIP1 c.10_13delGTCT (p.Val4LeufsX9) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic in ClinVar and is associated with Fraser syndrome in HGMD. The variant was absent in 248788 control chromosomes (gnomAD). To our knowledge, no occurrence of c.10_13delGTCT in individuals affected with Cryptophthalmos Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 5, 2023

ClinVar

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