2-216117647-C-G

Variant names:

• chr2-216117647-C-G
• rs3815855
• ENST00000460284.5:n.763C>G

Variant summary

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

The ENST00000460284.5(XRCC5):​n.763C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,203,820 control chromosomes in the GnomAD database, including 24,822 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 0.19 (2903 hom., cov: 32)
  • Exomes 𝑓: 0.20 (21919 hom.)
• Consequence: XRCC5 ENST00000460284.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000460284.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC5	NM_021141.4	MANE Select	c.320-99C>G		intron	N/A	NP_066964.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC5	ENST00000460284.5	TSL:1	n.763C>G		non_coding_transcript_exon	Exon 1 of 18
	XRCC5	ENST00000392132.7	TSL:1 MANE Select	c.320-99C>G		intron	N/A	ENSP00000375977.2
	XRCC5	ENST00000392133.7	TSL:5	c.320-99C>G		intron	N/A	ENSP00000375978.3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29580 AN: 152006 Hom.: 2901 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.200

GnomAD4 exome AF: 0.201 AC: 211727 AN: 1051696 Hom.: 21919 Cov.: 13 AF XY: 0.200 AC XY: 107170 AN XY: 536730

African (AFR) AF: 0.157 AC: 3955 AN: 25202

American (AMR) AF: 0.215 AC: 9108 AN: 42452

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 5877 AN: 22972

East Asian (EAS) AF: 0.125 AC: 4594 AN: 36634

South Asian (SAS) AF: 0.141 AC: 10651 AN: 75662

European-Finnish (FIN) AF: 0.261 AC: 13399 AN: 51258

Middle Eastern (MID) AF: 0.213 AC: 1048 AN: 4930

European-Non Finnish (NFE) AF: 0.206 AC: 153816 AN: 746248

Other (OTH) AF: 0.200 AC: 9279 AN: 46338

GnomAD4 genome AF: 0.195 AC: 29592 AN: 152124 Hom.: 2903 Cov.: 32 AF XY: 0.197 AC XY: 14643 AN XY: 74354

African (AFR) AF: 0.156 AC: 6492 AN: 41488

American (AMR) AF: 0.200 AC: 3059 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3472

East Asian (EAS) AF: 0.172 AC: 893 AN: 5182

South Asian (SAS) AF: 0.147 AC: 710 AN: 4824

European-Finnish (FIN) AF: 0.268 AC: 2827 AN: 10568

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14056 AN: 67994

Other (OTH) AF: 0.198 AC: 418 AN: 2108

Alfa AF: 0.198 Hom.: 381

Bravo AF: 0.192

Asia WGS AF: 0.143 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.4
DANN	Benign	0.52
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs3815855; hg19: chr2-216982370; COSMIC: COSV67536994; COSMIC: COSV67536994;