NM_005219.5(DIAPH1):c.147G>A (p.Leu49=) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 25, 2023
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:: RCV003802296.1

Allele description [Variation Report for NM_005219.5(DIAPH1):c.147G>A (p.Leu49=)]

NM_005219.5(DIAPH1):c.147G>A (p.Leu49=)

Gene:

DIAPH1:diaphanous related formin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q31.3

Genomic location:

Preferred name:

NM_005219.5(DIAPH1):c.147G>A (p.Leu49=)

HGVS:

NC_000005.10:g.141587195C>T
NG_011594.2:g.36861G>A
NM_001079812.3:c.120G>A
NM_001314007.2:c.147G>A
NM_005219.5:c.147G>AMANE SELECT
NP_001073280.1:p.Leu40=
NP_001300936.1:p.Leu49=
NP_005210.3:p.Leu49=
LRG_1117t1:c.120G>A
LRG_1117t2:c.147G>A
LRG_1117:g.36861G>A
LRG_1117p1:p.Leu40=
LRG_1117p2:p.Leu49=
NC_000005.9:g.140966762C>T

Molecular consequence:

NM_001079812.3:c.120G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001314007.2:c.147G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_005219.5:c.147G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Autosomal dominant nonsyndromic hearing loss 1
Synonyms:: KONIGSMARK SYNDROME; Deafness, autosomal dominant 1; DEAFNESS, AUTOSOMAL DOMINANT 1, WITH OR WITHOUT THROMBOCYTOPENIA
Identifiers:: MONDO: MONDO:0007424; MedGen: C1852282; Orphanet: 90635; OMIM: 124900

Name:: Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome
Synonyms:: Seizures, cortical blindness, and microcephaly syndrome
Identifiers:: MONDO: MONDO:0014714; MedGen: C5567650; OMIM: 616632

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004608888	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 25, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004608888

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 25, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004608888.1

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

Description

This sequence change affects codon 49 of the DIAPH1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the DIAPH1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DIAPH1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Mar 5, 2024

ClinVar

Relating variation to medicine