7-152648413-GAAAAAAA-GAAAA

Variant names:

• chr7-152648413-GAAA-G
• rs10707642
• NM_005431.2:c.*226_*228delTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_005431.2(XRCC2):​c.*226_*228delTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00492 in 259,702 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000064 (0 hom., cov: 0)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: XRCC2 NM_005431.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

Genes affected

XRCC2 (HGNC:12829): (X-ray repair cross complementing 2) This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene is involved in the repair of DNA double-strand breaks by homologous recombination and it functionally complements Chinese hamster irs1, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0107 (1270/118226) while in subpopulation SAS AF= 0.0144 (51/3548). AF 95% confidence interval is 0.0112. There are 0 homozygotes in gnomad4_exome. There are 655 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC2	NM_005431.2	c.*226_*228delTTT		3_prime_UTR_variant	Exon 3 of 3	ENST00000359321.2	NP_005422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC2	ENST00000359321	c.*226_*228delTTT		3_prime_UTR_variant	Exon 3 of 3	1	NM_005431.2	ENSP00000352271.1
XRCC2	ENST00000495707.1	n.1091_1093delTTT		non_coding_transcript_exon_variant	Exon 3 of 3	1
XRCC2	ENST00000698506	c.*226_*228delTTT		3_prime_UTR_variant	Exon 2 of 2			ENSP00000513758.1

Frequencies

GnomAD3 genomes AF: 0.0000636 AC: 9 AN: 141476 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000705

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000357

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000458

Gnomad OTH AF: 0.000518

GnomAD4 exome AF: 0.0107 AC: 1270 AN: 118226 Hom.: 0 AF XY: 0.0111 AC XY: 655 AN XY: 58764

Gnomad4 AFR exome AF: 0.00454

Gnomad4 AMR exome AF: 0.0101

Gnomad4 ASJ exome AF: 0.00755

Gnomad4 EAS exome AF: 0.00595

Gnomad4 SAS exome AF: 0.0144

Gnomad4 FIN exome AF: 0.0166

Gnomad4 NFE exome AF: 0.0115

Gnomad4 OTH exome AF: 0.0103

GnomAD4 genome AF: 0.0000636 AC: 9 AN: 141476 Hom.: 0 Cov.: 0 AF XY: 0.0000585 AC XY: 4 AN XY: 68336

Gnomad4 AFR AF: 0.0000265

Gnomad4 AMR AF: 0.0000705

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000357

Gnomad4 NFE AF: 0.0000458

Gnomad4 OTH AF: 0.000518

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs10707642; hg19: chr7-152345498;