2-17532533-T-C

Variant names:

• chr2-17532533-T-C
• rs424827
• XM_047445730.1:c.-12222A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047445730.1(RAD51AP2):​c.-12222A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,832 control chromosomes in the GnomAD database, including 26,902 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (26902 hom., cov: 31)
• Consequence: RAD51AP2 XM_047445730.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 7 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]

ENSG00000308172 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51AP2	XM_047445730.1	c.-12222A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6		XP_047301686.1
RAD51AP2	XM_047445730.1	c.-12222A>G		5_prime_UTR_variant	Exon 1 of 6		XP_047301686.1
RAD51AP2	XM_024453116.2	c.-409-2119A>G		intron_variant	Intron 1 of 7		XP_024308884.1
RAD51AP2	XM_024453117.2	c.-409-2119A>G		intron_variant	Intron 1 of 7		XP_024308885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000308172	ENST00000832128.1	n.291+13605T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85265 AN: 151716 Hom.: 26895 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.609

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.562 AC: 85294 AN: 151832 Hom.: 26902 Cov.: 31 AF XY: 0.571 AC XY: 42382 AN XY: 74190

African (AFR) AF: 0.257 AC: 10617 AN: 41334

American (AMR) AF: 0.683 AC: 10418 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2140 AN: 3470

East Asian (EAS) AF: 0.885 AC: 4574 AN: 5166

South Asian (SAS) AF: 0.809 AC: 3892 AN: 4812

European-Finnish (FIN) AF: 0.690 AC: 7266 AN: 10538

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.651 AC: 44202 AN: 67946

Other (OTH) AF: 0.612 AC: 1288 AN: 2104

Alfa AF: 0.635 Hom.: 15820

Bravo AF: 0.548

Asia WGS AF: 0.821 AC: 2851 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.49
DANN	Benign	0.57
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs424827; hg19: chr2-17713800;