17-35100938-AAAC-A

Variant names:

• chr17-35100938-AAAC-A
• rs745601646
• NM_002878.4:c.*12_*14delGTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_002878.4(RAD51D):​c.*12_*14delGTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,607,012 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RAD51D NM_002878.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.186
• Publications: 0 publications found

Genes affected

RAD51D (HGNC:9823): (RAD51 paralog D) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and Saccharomyces cerevisiae Rad51, which are known to be involved in the homologous recombination and repair of DNA. This protein forms a complex with several other members of the RAD51 family, including RAD51L1, RAD51L2, and XRCC2. The protein complex formed with this protein has been shown to catalyze homologous pairing between single- and double-stranded DNA, and is thought to play a role in the early stage of recombinational repair of DNA. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream ring finger and FYVE-like domain containing 1 (RFFL) gene. [provided by RefSeq, Jan 2011]

RAD51D Gene-Disease associations (from GenCC):

• RAD51D-related cancer predisposition

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• breast-ovarian cancer, familial, susceptibility to, 4

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• hereditary breast ovarian cancer syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000267618 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 17-35100938-AAAC-A is Benign according to our data. Variant chr17-35100938-AAAC-A is described in ClinVar as Likely_benign. ClinVar VariationId is 421911.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002878.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51D	NM_002878.4	MANE Select	c.*12_*14delGTT		3_prime_UTR	Exon 10 of 10	NP_002869.3
	RAD51D	NM_001142571.2		c.*12_*14delGTT		3_prime_UTR	Exon 10 of 10	NP_001136043.1	O75771-8
	RAD51D	NM_133629.3		c.*12_*14delGTT		3_prime_UTR	Exon 7 of 7	NP_598332.1	O75771-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51D	ENST00000345365.11	TSL:1 MANE Select	c.*12_*14delGTT		3_prime_UTR	Exon 10 of 10	ENSP00000338790.6	O75771-1
	RAD51D	ENST00000586186.3	TSL:1	c.*12_*14delGTT		3_prime_UTR	Exon 9 of 9	ENSP00000468273.3	O75771-4
	RAD51D	ENST00000335858.11	TSL:1	c.*12_*14delGTT		3_prime_UTR	Exon 7 of 7	ENSP00000338408.6	O75771-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454866 Hom.: 0 AF XY: 0.00000138 AC XY: 1 AN XY: 724318

African (AFR) AF: 0.00 AC: 0 AN: 33276

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5630

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105814

Other (OTH) AF: 0.0000166 AC: 1 AN: 60142

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74314

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs745601646; hg19: chr17-33427957;