NM_004086.3(COCH):c.841G>A (p.Asp281Asn) AND not provided

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Dec 22, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000755937.17

Allele description [Variation Report for NM_004086.3(COCH):c.841G>A (p.Asp281Asn)]

NM_004086.3(COCH):c.841G>A (p.Asp281Asn)

Genes:

COCH:cochlin [Gene - OMIM - HGNC]
LOC100506071:uncharacterized LOC100506071 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

14q12

Genomic location:

Preferred name:

NM_004086.3(COCH):c.841G>A (p.Asp281Asn)

Other names:

NM_004086.2(COCH):c.841G>A

HGVS:

NC_000014.9:g.30885501G>A
NG_008211.2:g.15967G>A
NM_001135058.2:c.841G>A
NM_001347720.2:c.1036G>A
NM_004086.3:c.841G>AMANE SELECT
NP_001128530.1:p.Asp281Asn
NP_001334649.1:p.Asp346Asn
NP_004077.1:p.Asp281Asn
NC_000014.8:g.31354707G>A
NM_004086.2:c.841G>A
NR_038356.1:n.1364C>T
O43405:p.Asp281Asn

Protein change:

D281N

Links:

UniProtKB: O43405#VAR_022260; dbSNP: rs28362775

NCBI 1000 Genomes Browser:

rs28362775

Molecular consequence:

NM_001135058.2:c.841G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001347720.2:c.1036G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004086.3:c.841G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_038356.1:n.1364C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000883616	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Likely benign (Oct 3, 2017)	germline	clinical testing	Citation Link,
SCV001068453	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Dec 22, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001867958	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Benign (Jan 15, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000883616

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Likely benign
(Oct 3, 2017)

germline

clinical testing

Citation Link,

SCV001068453

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Dec 22, 2023)

germline

clinical testing

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

SCV001867958

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Benign
(Jan 15, 2019)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000883616.1

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

Description

The c.841G>A; p.Asp281Asn variant (rs28362775) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.6 percent in the African population (identified on 145 out of 24,032 chromosomes), and has been reported to the ClinVar database (Variation ID: 226529). The aspartic acid at position 281 is moderately conserved across 12 species (Alamut v2.9.0) and computational analyses of the effects of the p.Asp281Asn variant on protein structure and function indicate a neutral effect (SIFT: tolerated, Align GVGD: C0, PolyPhen-2: benign). Based on these observations the p.Asp281Asn is likely to be benign.

#	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

From Invitae, SCV001068453.4

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

#	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

From GeneDx, SCV001867958.1

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

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

Last Updated: Feb 20, 2024

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