rs11685387

Variant names:

• chr2-216109091-C-G
• rs11685387
• ENST00000392133.7:c.-346C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-216109091-C-G
• chr2-216109091-C-T

Variant summary

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

The ENST00000392133.7(XRCC5):​c.-346C>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000914 in 1,094,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: XRCC5 ENST00000392133.7 splice_region
• Scores: Splicing: ADA: 0.000008232
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 21 publications found

Genes affected

XRCC5 (HGNC:12833): (X-ray repair cross complementing 5) The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. This gene functionally complements Chinese hamster xrs-6, a mutant defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

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 (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000392133.7. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC5	ENST00000392133.7	TSL:5	c.-346C>G		splice_region	Exon 3 of 23	ENSP00000375978.3	P13010
	XRCC5	ENST00000392133.7	TSL:5	c.-346C>G		5_prime_UTR	Exon 3 of 23	ENSP00000375978.3	P13010
	XRCC5	ENST00000939180.1		c.-346C>G		upstream_gene	N/A	ENSP00000609239.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 9.14e-7 AC: 1 AN: 1094644 Hom.: 0 Cov.: 29 AF XY: 0.00000191 AC XY: 1 AN XY: 524644

African (AFR) AF: 0.00 AC: 0 AN: 23010

American (AMR) AF: 0.00 AC: 0 AN: 13404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12468

East Asian (EAS) AF: 0.00 AC: 0 AN: 18718

South Asian (SAS) AF: 0.00 AC: 0 AN: 59806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2616

European-Non Finnish (NFE) AF: 0.00000110 AC: 1 AN: 910168

Other (OTH) AF: 0.00 AC: 0 AN: 41374

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 4256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.47
DANN	Benign	0.54
PhyloP100		-1.3
PromoterAI		-0.076	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000082
dbscSNV1_RF	Benign	0.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11685387;

hg19: chr2-216973814;