Genetic Variant NM_005431.2:c.*222_*228delTTTTTTT (chr7-152648413-GAAAAAAA-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_005431.2(XRCC2):c.*222_*228delTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000071 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

XRCC2
NM_005431.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.347

Publications

0 publications found

Variant links:

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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
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

XRCC2 links:

ENSG00000298894 (HGNC:):

ENSG00000298894 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005431.2. 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
	XRCC2	NM_005431.2	MANE Select	c.222_228delTTTTTTT		3_prime_UTR	Exon 3 of 3	NP_005422.1	O43543

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
XRCC2	ENST00000359321.2	TSL:1 MANE Select	c.222_228delTTTTTTT	3_prime_UTR	Exon 3 of 3	ENSP00000352271.1	O43543
XRCC2	ENST00000495707.1	TSL:1	n.1087_1093delTTTTTTT	non_coding_transcript_exon	Exon 3 of 3
XRCC2	ENST00000698506.1		c.222_228delTTTTTTT	3_prime_UTR	Exon 2 of 2	ENSP00000513758.1	A0A8V8TMB7

Frequencies

GnomAD3 genomes

AF:

0.00000707

AC:

AN:

141494

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

119238

Hom.:

AF XY:

0.00

AC XY:

AN XY:

59268

African (AFR)

AF:

0.00

AC:

AN:

3994

American (AMR)

AF:

0.00

AC:

AN:

4580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4950

East Asian (EAS)

AF:

0.00

AC:

AN:

10538

South Asian (SAS)

AF:

0.00

AC:

AN:

3584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4666

Middle Eastern (MID)

AF:

0.00

AC:

AN:

628

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

78074

Other (OTH)

AF:

0.00

AC:

AN:

8224

GnomAD4 genome

AF:

0.00000707

AC:

AN:

141494

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68354

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

37690

American (AMR)

AF:

0.0000705

AC:

AN:

14190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3340

East Asian (EAS)

AF:

0.00

AC:

AN:

4794

South Asian (SAS)

AF:

0.00

AC:

AN:

4490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65482

Other (OTH)

AF:

0.00

AC:

AN:

1932

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

839

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.35

Splicing

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.

Publications

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NM_005431.2:c.222_228delTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over