rs140673266

Variant names:

• chr2-17515535-C-A
• rs140673266
• NM_001099218.3:c.2881G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-17515535-C-A
• chr2-17515535-C-G
• chr2-17515535-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001099218.3(RAD51AP2):​c.2881G>T​(p.Asp961Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,608,652 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00010 (1 hom.)
• Consequence: RAD51AP2 NM_001099218.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.788
• Publications: 2 publications found

Genes affected

RAD51AP2 (HGNC:34417): (RAD51 associated protein 2) Predicted to enable double-stranded DNA binding activity and single-stranded DNA binding activity. Predicted to be involved in double-strand break repair via homologous recombination and interstrand cross-link repair. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040083766).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099218.3. 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
	RAD51AP2	NM_001099218.3	MANE Select	c.2881G>T	p.Asp961Tyr	missense	Exon 1 of 3	NP_001092688.1	Q09MP3
	RAD51AP2	NM_001321233.1		c.2854G>T	p.Asp952Tyr	missense	Exon 5 of 7	NP_001308162.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51AP2	ENST00000399080.3	TSL:1 MANE Select	c.2881G>T	p.Asp961Tyr	missense	Exon 1 of 3	ENSP00000382030.2	Q09MP3

Frequencies

GnomAD3 genomes AF: 0.000513 AC: 78 AN: 152130 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

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: 0.000132

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000206 AC: 50 AN: 242368 AF XY: 0.000175

Gnomad AFR exome AF: 0.00158

Gnomad AMR exome AF: 0.000360

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000992

Gnomad OTH exome AF: 0.000509

GnomAD4 exome AF: 0.000104 AC: 151 AN: 1456404 Hom.: 1 Cov.: 34 AF XY: 0.0000842 AC XY: 61 AN XY: 724188

African (AFR) AF: 0.00157 AC: 52 AN: 33032

American (AMR) AF: 0.000413 AC: 18 AN: 43594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25938

East Asian (EAS) AF: 0.00 AC: 0 AN: 39602

South Asian (SAS) AF: 0.00 AC: 0 AN: 84414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5732

European-Non Finnish (NFE) AF: 0.0000549 AC: 61 AN: 1110572

Other (OTH) AF: 0.000299 AC: 18 AN: 60172

GnomAD4 genome AF: 0.000512 AC: 78 AN: 152248 Hom.: 0 Cov.: 33 AF XY: 0.000551 AC XY: 41 AN XY: 74456

African (AFR) AF: 0.00142 AC: 59 AN: 41576

American (AMR) AF: 0.000523 AC: 8 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67984

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000299 Hom.: 0

Bravo AF: 0.000563

ESP6500AA AF: 0.000556 AC: 2

ESP6500EA AF: 0.000246 AC: 2

ExAC AF: 0.000232 AC: 28

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.061
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.79
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Benign	0.13
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.51
MVP		0.47
MPC		0.36
ClinPred		0.096	T
GERP RS		3.4
Varity_R		0.33
gMVP		0.36
Mutation Taster		=97/3	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

Other links and lift over

dbSNP: rs140673266; hg19: chr2-17696802; COSMIC: COSV101208384;