NM_005219.5(DIAPH1):c.3167A>C (p.Gln1056Pro) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 19, 2024
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:: RCV001997620.5

Allele description [Variation Report for NM_005219.5(DIAPH1):c.3167A>C (p.Gln1056Pro)]

NM_005219.5(DIAPH1):c.3167A>C (p.Gln1056Pro)

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.3167A>C (p.Gln1056Pro)

HGVS:

NC_000005.10:g.141527679T>G
NG_011594.2:g.96377A>C
NM_001079812.3:c.3140A>C
NM_001314007.2:c.3167A>C
NM_005219.5:c.3167A>CMANE SELECT
NP_001073280.1:p.Gln1047Pro
NP_001300936.1:p.Gln1056Pro
NP_005210.3:p.Gln1056Pro
LRG_1117t1:c.3140A>C
LRG_1117t2:c.3167A>C
LRG_1117:g.96377A>C
LRG_1117p1:p.Gln1047Pro
LRG_1117p2:p.Gln1056Pro
NC_000005.9:g.140907246T>G

Protein change:

Q1047P

Links:

dbSNP: rs2154594980

NCBI 1000 Genomes Browser:

rs2154594980

Molecular consequence:

NM_001079812.3:c.3140A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001314007.2:c.3167A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005219.5:c.3167A>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002230409	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 19, 2024)	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

SCV002230409

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 19, 2024)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002230409.4

#	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 replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1056 of the DIAPH1 protein (p.Gln1056Pro). 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. ClinVar contains an entry for this variant (Variation ID: 1449581). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 11, 2025

ClinVar

Relating variation to medicine