2-167006910-T-C

Variant names:

• chr2-167006910-T-C
• rs1877192
• NM_152381.6:c.408+103020T>C

Variant summary

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

The NM_152381.6(XIRP2):​c.408+103020T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,502 control chromosomes in the GnomAD database, including 3,709 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 (3709 hom., cov: 32)
• Consequence: XIRP2 NM_152381.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152381.6. 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
	XIRP2	NM_152381.6	MANE Select	c.408+103020T>C		intron	N/A	NP_689594.4
	XIRP2	NM_001199143.2		c.408+103020T>C		intron	N/A	NP_001186072.1
	XIRP2	NM_001079810.4		c.408+103020T>C		intron	N/A	NP_001073278.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIRP2	ENST00000409195.6	TSL:5 MANE Select	c.408+103020T>C		intron	N/A	ENSP00000386840.2
	XIRP2	ENST00000409728.5	TSL:1	c.408+103020T>C		intron	N/A	ENSP00000386619.1
	XIRP2	ENST00000409043.5	TSL:1	c.408+103020T>C		intron	N/A	ENSP00000386454.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29023 AN: 151384 Hom.: 3687 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.192 AC: 29113 AN: 151502 Hom.: 3709 Cov.: 32 AF XY: 0.198 AC XY: 14675 AN XY: 74004

African (AFR) AF: 0.252 AC: 10417 AN: 41376

American (AMR) AF: 0.234 AC: 3537 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 375 AN: 3458

East Asian (EAS) AF: 0.678 AC: 3467 AN: 5116

South Asian (SAS) AF: 0.230 AC: 1109 AN: 4820

European-Finnish (FIN) AF: 0.150 AC: 1587 AN: 10560

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8160 AN: 67740

Other (OTH) AF: 0.188 AC: 395 AN: 2096

Alfa AF: 0.145 Hom.: 5857

Bravo AF: 0.202

Asia WGS AF: 0.417 AC: 1444 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.1
DANN	Benign	0.74
PhyloP100		0.054
Mutation Taster		=100/0	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: rs1877192; hg19: chr2-167863420;