VCV002709440.2 - ClinVar

NM_002878.4(RAD51D):c.970C>T (p.Gln324Ter)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(2)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Uncertain significance

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_002878.4(RAD51D):c.970C>T (p.Gln324Ter)

Variation ID: 2709440 Accession: VCV002709440.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q12 17: 35100970 (GRCh38) [ NCBI UCSC ] 17: 33427989 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 14, 2024	May 1, 2024	Feb 26, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_002878.4:c.970C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002869.3:p.Gln324Ter	nonsense
NM_001142571.2:c.1030C>T	NP_001136043.1:p.Gln344Ter	nonsense
NM_133629.3:c.634C>T	NP_598332.1:p.Gln212Ter	nonsense
NR_037711.2:n.996C>T		non-coding transcript variant
NR_037712.2:n.861C>T		non-coding transcript variant
NC_000017.11:g.35100970G>A
NC_000017.10:g.33427989G>A
NG_031858.1:g.23900C>T
LRG_516:g.23900C>T
LRG_516t1:c.970C>T	LRG_516p1:p.Gln324Ter

... more HGVS ... less HGVS

Protein change

Q212*, Q344*, Q324*

Other names

Canonical SPDI

NC_000017.11:35100969:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
RAD51D		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	34	1820
RAD51L3-RFFL	-	-	-	GRCh38	-	1799

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Breast-ovarian cancer, familial, susceptibility to, 4	Uncertain significance (1)	criteria provided, single submitter	Jan 15, 2024	RCV003528937.2
Hereditary cancer-predisposing syndrome	Uncertain significance (1)	criteria provided, single submitter	Feb 26, 2024	RCV004369006.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Jan 15, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 4 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004260039.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024	Comment: This sequence change creates a premature translational stop signal (p.Gln324) in the RAD51D gene. While this is not anticipated to result in nonsense mediated decay, … (more) This sequence change creates a premature translational stop signal (p.Gln324) in the RAD51D gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 5 amino acid(s) of the RAD51D protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. (less)
Uncertain significance (Feb 26, 2024)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV005019445.1 First in ClinVar: May 01, 2024 Last updated: May 01, 2024	Comment: The p.Q324* variant (also known as c.970C>T), located in coding exon 10 of the RAD51D gene, results from a C to T substitution at nucleotide … (more) The p.Q324* variant (also known as c.970C>T), located in coding exon 10 of the RAD51D gene, results from a C to T substitution at nucleotide position 970. This changes the amino acid from a glutamine to a stop codon within coding exon 10. This alteration occurs at the 3' terminus of theRAD51D gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 5 amino acids of the protein. The exact functional effect of this alteration is unknown. Based on the available evidence, the clinical significance of this alteration remains unclear. (less)

Comment:

This sequence change creates a premature translational stop signal (p.Gln324*) in the RAD51D gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 5 amino acid(s) of the RAD51D protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.

Comment:

The p.Q324* variant (also known as c.970C>T), located in coding exon 10 of the RAD51D gene, results from a C to T substitution at nucleotide position 970. This changes the amino acid from a glutamine to a stop codon within coding exon 10. This alteration occurs at the 3' terminus of theRAD51D gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 5 amino acids of the protein. The exact functional effect of this alteration is unknown. Based on the available evidence, the clinical significance of this alteration remains unclear.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NM_002878.4(RAD51D):c.970C>T (p.Gln324Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...