NM_005219.5(DIAPH1):c.2061C>G (p.Ile687Met) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 2, 2021
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:: RCV001940540.6

Allele description [Variation Report for NM_005219.5(DIAPH1):c.2061C>G (p.Ile687Met)]

NM_005219.5(DIAPH1):c.2061C>G (p.Ile687Met)

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.2061C>G (p.Ile687Met)

HGVS:

NC_000005.10:g.141573789G>C
NG_011594.2:g.50267C>G
NM_001079812.3:c.2034C>G
NM_001314007.2:c.2061C>G
NM_005219.5:c.2061C>GMANE SELECT
NP_001073280.1:p.Ile678Met
NP_001300936.1:p.Ile687Met
NP_005210.3:p.Ile687Met
LRG_1117t1:c.2034C>G
LRG_1117t2:c.2061C>G
LRG_1117:g.50267C>G
LRG_1117p1:p.Ile678Met
LRG_1117p2:p.Ile687Met
NC_000005.9:g.140953356G>C

Protein change:

I678M

Links:

dbSNP: rs1436744741

NCBI 1000 Genomes Browser:

rs1436744741

Molecular consequence:

NM_001079812.3:c.2034C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001314007.2:c.2061C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_005219.5:c.2061C>G - 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

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NADH dehydrogenase subunit 6 (mitochondrion) [Bunaea alcinoe]
NADH dehydrogenase subunit 6 (mitochondrion) [Bunaea alcinoe]
gi|2198384018|gb|ULO26033.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002192311	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 2, 2021)	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

SCV002192311

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 2, 2021)

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, SCV002192311.3

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with DIAPH1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces isoleucine with methionine at codon 687 of the DIAPH1 protein (p.Ile687Met). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and methionine.

#	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: Sep 29, 2024

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