chr2-167243228-T-C

Variant names:

• chr2-167243228-T-C
• rs10497323
• NM_152381.6:c.1836T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_152381.6(XIRP2):​c.1836T>C​(p.Gly612Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,613,762 control chromosomes in the GnomAD database, including 36,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.28 (7638 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29249 hom.)
• Consequence: XIRP2 NM_152381.6 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.321
• Publications: 16 publications found

Genes affected

XIRP2 (HGNC:14303): (xin actin binding repeat containing 2) Enables actin filament binding activity. Predicted to be involved in actin cytoskeleton organization and heart development. Predicted to act upstream of or within cardiac muscle tissue morphogenesis; cell-cell junction organization; and ventricular septum development. Colocalizes with focal adhesion and stress fiber. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 2-167243228-T-C is Benign according to our data. Variant chr2-167243228-T-C is described in ClinVar as Benign. ClinVar VariationId is 3058991.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.321 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XIRP2	NM_152381.6	c.1836T>C	p.Gly612Gly	synonymous_variant	Exon 9 of 11	ENST00000409195.6	NP_689594.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XIRP2	ENST00000409195.6	c.1836T>C	p.Gly612Gly	synonymous_variant	Exon 9 of 11	5	NM_152381.6	ENSP00000386840.2

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42180 AN: 151860 Hom.: 7605 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.247

GnomAD2 exomes AF: 0.225 AC: 56032 AN: 249314 AF XY: 0.222

Gnomad AFR exome AF: 0.523

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.303

Gnomad FIN exome AF: 0.216

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.200

GnomAD4 exome AF: 0.185 AC: 271133 AN: 1461784 Hom.: 29249 Cov.: 36 AF XY: 0.187 AC XY: 135920 AN XY: 727194

African (AFR) AF: 0.526 AC: 17615 AN: 33478

American (AMR) AF: 0.230 AC: 10289 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 4201 AN: 26136

East Asian (EAS) AF: 0.349 AC: 13864 AN: 39698

South Asian (SAS) AF: 0.299 AC: 25750 AN: 86254

European-Finnish (FIN) AF: 0.211 AC: 11295 AN: 53414

Middle Eastern (MID) AF: 0.193 AC: 1113 AN: 5768

European-Non Finnish (NFE) AF: 0.157 AC: 174617 AN: 1111922

Other (OTH) AF: 0.205 AC: 12389 AN: 60394

GnomAD4 genome AF: 0.278 AC: 42273 AN: 151978 Hom.: 7638 Cov.: 32 AF XY: 0.279 AC XY: 20756 AN XY: 74268

African (AFR) AF: 0.512 AC: 21192 AN: 41430

American (AMR) AF: 0.236 AC: 3611 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3470

East Asian (EAS) AF: 0.309 AC: 1586 AN: 5128

South Asian (SAS) AF: 0.308 AC: 1483 AN: 4808

European-Finnish (FIN) AF: 0.212 AC: 2242 AN: 10566

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10932 AN: 67976

Other (OTH) AF: 0.248 AC: 524 AN: 2114

Alfa AF: 0.201 Hom.: 6344

Bravo AF: 0.287

Asia WGS AF: 0.339 AC: 1181 AN: 3478

EpiCase AF: 0.158

EpiControl AF: 0.148

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

XIRP2-related disorder Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	2.3
DANN	Benign	0.55
PhyloP100		0.32
Mutation Taster		=99/1	polymorphism (auto)

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: rs10497323; hg19: chr2-168099738; COSMIC: COSV54700799;