NM_002878.4(RAD51D):c.408T>A (p.Asp136Glu) AND Breast-ovarian cancer, familial, susceptibility to, 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 27, 2019
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:: RCV001203987.5

Allele description [Variation Report for NM_002878.4(RAD51D):c.408T>A (p.Asp136Glu)]

NM_002878.4(RAD51D):c.408T>A (p.Asp136Glu)

Genes:

RAD51D:RAD51 paralog D [Gene - OMIM - HGNC]
RAD51L3-RFFL:RAD51L3-RFFL readthrough [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

17q12

Genomic location:

Preferred name:

NM_002878.4(RAD51D):c.408T>A (p.Asp136Glu)

HGVS:

NC_000017.11:g.35107060A>T
NG_031858.1:g.17810T>A
NM_001142571.2:c.468T>A
NM_002878.4:c.408T>AMANE SELECT
NM_133629.3:c.145-579T>A
NP_001136043.1:p.Asp156Glu
NP_002869.3:p.Asp136Glu
NP_002869.3:p.Asp136Glu
LRG_516t1:c.408T>A
LRG_516:g.17810T>A
LRG_516p1:p.Asp136Glu
NC_000017.10:g.33434079A>T
NM_002878.3:c.408T>A
NR_037711.2:n.434T>A

Protein change:

D136E

Links:

dbSNP: rs1567728349

NCBI 1000 Genomes Browser:

rs1567728349

Molecular consequence:

NM_133629.3:c.145-579T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001142571.2:c.468T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002878.4:c.408T>A - missense variant - [Sequence Ontology: SO:0001583]
NR_037711.2:n.434T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Breast-ovarian cancer, familial, susceptibility to, 4
Synonyms:: Breast-ovarian cancer, familial 4
Identifiers:: MONDO: MONDO:0013669; MedGen: C3280345; Orphanet: 145; OMIM: 614291

Recent activity

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zinc finger and BTB domain-containing protein 18 isoform X1 [Homo sapiens]
zinc finger and BTB domain-containing protein 18 isoform X1 [Homo sapiens]
gi|2217263198|ref|XP_047286880.1|

Protein
Mus musculus cytosolic iron-sulfur assembly component 2A (Ciao2a), transcript va...
Mus musculus cytosolic iron-sulfur assembly component 2A (Ciao2a), transcript variant 1, mRNA
gi|71773979|ref|NM_026635.3|

Nucleotide
Mus musculus clone 220n14 Naip2 gene, partial sequence
Mus musculus clone 220n14 Naip2 gene, partial sequence
gi|8895967|gb|AF240494.1|AF240494

Nucleotide
Marchantia polymorpha strain Tak-1 unplaced genomic scaffold scaffold_92, whole ...
Marchantia polymorpha strain Tak-1 unplaced genomic scaffold scaffold_92, whole genome shotgun sequence
gi|1376842378|gb|KZ772764.1||gnl|WG G01|scaffold_92

Nucleotide
P20 protein, partial [Bamboo mosaic virus satellite RNA]
P20 protein, partial [Bamboo mosaic virus satellite RNA]
gi|757819616|gb|AJO26616.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001375172	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 27, 2019)	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

SCV001375172

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 27, 2019)

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, SCV001375172.4

#	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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RAD51D-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glutamic acid at codon 136 of the RAD51D protein (p.Asp136Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid.

#	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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