rs207936

Variant names:

• chr2-216175310-C-A
• rs207936
• NM_021141.4:c.1834+13262C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-216175310-C-A
• chr2-216175310-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021141.4(XRCC5):​c.1834+13262C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000333 in 300,606 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 0 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]

ENSG00000236478 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.1834+13262C>A		intron_variant	Intron 16 of 20	ENST00000392132.7	NP_066964.1
LOC100421349		n.216175310C>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC5	ENST00000392132.7	c.1834+13262C>A		intron_variant	Intron 16 of 20	1	NM_021141.4	ENSP00000375977.2
XRCC5	ENST00000460284.5	n.2376+13262C>A		intron_variant	Intron 13 of 17	1
ENSG00000236478	ENST00000441511.2	n.723G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
XRCC5	ENST00000392133.7	c.1834+13262C>A		intron_variant	Intron 18 of 22	5		ENSP00000375978.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000333 AC: 1 AN: 300606 Hom.: 0 Cov.: 0 AF XY: 0.00000579 AC XY: 1 AN XY: 172676

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 7956

American (AMR) AF: 0.00 AC: 0 AN: 24700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7038

East Asian (EAS) AF: 0.00 AC: 0 AN: 12438

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 54146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1042

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 163540

Other (OTH) AF: 0.00 AC: 0 AN: 13772

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs207936; hg19: chr2-217040033;