rs1422741411

Variant names:

• chr2-17515607-C-T
• rs1422741411
• NM_001099218.3:c.2809G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001099218.3(RAD51AP2):​c.2809G>A​(p.Glu937Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: RAD51AP2 NM_001099218.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.266
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.017257571).

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.2809G>A	p.Glu937Lys	missense	Exon 1 of 3	NP_001092688.1	Q09MP3
	RAD51AP2	NM_001321233.1		c.2782G>A	p.Glu928Lys	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.2809G>A	p.Glu937Lys	missense	Exon 1 of 3	ENSP00000382030.2	Q09MP3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000813 AC: 2 AN: 246120 AF XY: 0.00000749

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000112

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1458368 Hom.: 0 Cov.: 34 AF XY: 0.00000276 AC XY: 2 AN XY: 725306

African (AFR) AF: 0.00 AC: 0 AN: 33310

American (AMR) AF: 0.00 AC: 0 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39612

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110592

Other (OTH) AF: 0.00 AC: 0 AN: 60256

GnomAD4 genome Cov.: 33

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	0.075
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.1
DANN	Benign	0.49
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.27
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.051
Sift	Benign	0.91	T
Sift4G	Benign	0.78	T
Polyphen		0.019	B
Vest4		0.11
MutPred		0.36		Gain of ubiquitination at E937 (P = 0.0082)
MVP		0.061
MPC		0.086
ClinPred		0.022	T
GERP RS		-0.12
Varity_R		0.029
gMVP		0.10
Mutation Taster		=100/0	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: rs1422741411; hg19: chr2-17696874; COSMIC: COSV105936888;