rs3218501

Variant names:

• chr7-152654832-G-A
• rs3218501
• NM_005431.2:c.122-5469C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-152654832-G-A
• chr7-152654832-G-C

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NM_005431.2(XRCC2):c.122-5469C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) 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: 33)
• Consequence: XRCC2 NM_005431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.904
• Publications: 6 publications found

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]

XRCC2 Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group U

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, LiferaOmics
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• premature ovarian failure 17

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• spermatogenic failure 50

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• breast cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000298894 (HGNC:):

Classification according to ACMG Germline Pathogenicity v2019

Our verdict: Likely_benign. The variant received -2 points.

• PM2: Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD+AR) (threshold 0.0001) — PM2 moderate.
• BP4: Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_005431.2. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC2	NM_005431.2	MANE Select	c.122-5469C>T		intron	N/A	NP_005422.1	A0A384MEK2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC2	ENST00000359321.2	TSL:1 MANE Select	c.122-5469C>T		intron	N/A	ENSP00000352271.1	O43543
	XRCC2	ENST00000495707.1	TSL:1	n.144-5469C>T		intron	N/A
	XRCC2	ENST00000698506.1		c.-47-5469C>T		intron	N/A	ENSP00000513758.1	A0A8V8TMB7

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

TOPMed (Bravo) AF: 0.0000151

ALFA (dbGaP/dbSNP Allele Frequency Aggregator) AF: 0.00 AC: 0 AN: 22684 Hom.: 42

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.59
PhyloP100		0.90
AlphaGenome AVI	Benign	5.5
GPN-Star LLR		-2.1
GPN-Star score		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2
Pangolin (max)	Benign	0.0

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: rs3218501;

hg19: chr7-152351917;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar