NM_002878.4(RAD51D):c.408T>A (p.Asp136Glu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 8, 2022
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:: RCV001178428.5

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:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

Clear Turn Off Turn On

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

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
SCV001342881	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 8, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002626550	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 8, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001342881

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 8, 2022)

germline

clinical testing

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

SCV002626550

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 8, 2021)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001342881.2

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

Description

This missense variant replaces aspartic acid with glutamic acid at codon 136 of the RAD51D protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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

From Ambry Genetics, SCV002626550.2

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

Description

The p.D136E variant (also known as c.408T>A), located in coding exon 5 of the RAD51D gene, results from a T to A substitution at nucleotide position 408. The aspartic acid at codon 136 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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

ClinVar

Relating variation to medicine