chr17-35117027-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000585343.5(RAD51D):​n.175C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,612,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

RAD51D
ENST00000585343.5 non_coding_transcript_exon

Scores

1
11

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.452

Publications

7 publications found
Variant links:
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):
  • breast-ovarian cancer, familial, susceptibility to, 4
    Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
  • hereditary breast ovarian cancer syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • hereditary breast carcinoma
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.005715817).
BP6
Variant 17-35117027-G-A is Benign according to our data. Variant chr17-35117027-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 492414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00023 (35/152158) while in subpopulation EAS AF = 0.00618 (32/5180). AF 95% confidence interval is 0.0045. There are 0 homozygotes in GnomAd4. There are 17 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAD51DNM_002878.4 linkc.263+1474C>T intron_variant Intron 3 of 9 ENST00000345365.11 NP_002869.3 O75771-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAD51DENST00000345365.11 linkc.263+1474C>T intron_variant Intron 3 of 9 1 NM_002878.4 ENSP00000338790.6 O75771-1
ENSG00000267618ENST00000593039.5 linkc.3+4264C>T intron_variant Intron 1 of 6 2 ENSP00000466834.1 K7EN88

Frequencies

GnomAD3 genomes
AF:
0.000230
AC:
35
AN:
152040
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00616
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000480
AC:
119
AN:
247924
AF XY:
0.000423
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00634
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000446
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000104
AC:
152
AN:
1460484
Hom.:
0
Cov.:
31
AF XY:
0.0000950
AC XY:
69
AN XY:
726356
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33460
American (AMR)
AF:
0.00
AC:
0
AN:
44676
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26056
East Asian (EAS)
AF:
0.00265
AC:
105
AN:
39674
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86198
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53378
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
0.0000288
AC:
32
AN:
1110964
Other (OTH)
AF:
0.000216
AC:
13
AN:
60318
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.482
Heterozygous variant carriers
0
8
16
25
33
41
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000230
AC:
35
AN:
152158
Hom.:
0
Cov.:
32
AF XY:
0.000228
AC XY:
17
AN XY:
74402
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41496
American (AMR)
AF:
0.00
AC:
0
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3466
East Asian (EAS)
AF:
0.00618
AC:
32
AN:
5180
South Asian (SAS)
AF:
0.000208
AC:
1
AN:
4812
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10602
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68000
Other (OTH)
AF:
0.00
AC:
0
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000111
Hom.:
0
Bravo
AF:
0.000204
ExAC
AF:
0.000299
AC:
36
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0000546
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
May 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

RAD51D: BP4, BS1 -

RAD51D-related disorder Benign:1
Apr 19, 2019
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hereditary cancer-predisposing syndrome Benign:1
Apr 21, 2015
Color Diagnostics, LLC DBA Color Health
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Breast-ovarian cancer, familial, susceptibility to, 4 Benign:1
May 22, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.70
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
7.6
DANN
Benign
0.65
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.025
N
LIST_S2
Benign
0.33
T
M_CAP
Pathogenic
0.36
D
MetaRNN
Benign
0.0057
T
MetaSVM
Benign
-0.94
T
PhyloP100
0.45
Sift4G
Benign
0.39
T
Vest4
0.18
MVP
0.28
MPC
0.32
ClinPred
0.084
T
GERP RS
-3.3
gMVP
0.47
Mutation Taster
=73/27
polymorphism

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

Publications

Other links and lift over

dbSNP: rs201720876; hg19: chr17-33444046; COSMIC: COSV50105567; COSMIC: COSV50105567; API