NM_032271.3(TRAF7):c.1964G>A (p.Arg655Gln) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 29, 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:: RCV001571649.7

Allele description [Variation Report for NM_032271.3(TRAF7):c.1964G>A (p.Arg655Gln)]

NM_032271.3(TRAF7):c.1964G>A (p.Arg655Gln)

Gene:

TRAF7:TNF receptor associated factor 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_032271.3(TRAF7):c.1964G>A (p.Arg655Gln)

Other names:

p.Arg655Gln

HGVS:

NC_000016.10:g.2176350G>A
NM_032271.3:c.1964G>AMANE SELECT
NP_115647.2:p.Arg655Gln
NC_000016.9:g.2226351G>A
NM_032271.2:c.1964G>A
p.R655Q

Protein change:

R655Q; ARG655GLN

Links:

OMIM: 606692.0001; dbSNP: rs1331463984

NCBI 1000 Genomes Browser:

rs1331463984

Molecular consequence:

NM_032271.3:c.1964G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001796158	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 29, 2023)	germline	clinical testing	Citation Link,
SCV003461737	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 10, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29961569, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001796158

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 29, 2023)

germline

clinical testing

Citation Link,

SCV003461737

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 10, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

De Novo Missense Variants in TRAF7 Cause Developmental Delay, Congenital Anomalies, and Dysmorphic Features.

Tokita MJ, Chen CA, Chitayat D, Macnamara E, Rosenfeld JA, Hanchard N, Lewis AM, Brown CW, Marom R, Shao Y, Novacic D, Wolfe L, Wahl C, Tifft CJ, Toro C, Bernstein JA, Hale CL, Silver J, Hudgins L, Ananth A, Hanson-Kahn A, Shuster S; et al.

Am J Hum Genet. 2018 Jul 5;103(1):154-162. doi: 10.1016/j.ajhg.2018.06.005. Epub 2018 Jun 28.

PubMed [citation]

PMID:: 29961569
PMCID:: PMC6035372

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 GeneDx, SCV001796158.2

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32459067, 31036916, 29961569, 25961944, 32376980, 28714951, 31981491, 32399599)

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003461737.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 655 of the TRAF7 protein (p.Arg655Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with TRAF7-related conditions (PMID: 29961569). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 587685). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects TRAF7 function (PMID: 29961569). For these reasons, this variant has been classified as 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: Sep 29, 2024

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