2-167250981-A-T

Position:

• chr2-167250981-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152381.6(XIRP2):​c.9589A>T​(p.Ile3197Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I3197V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: XIRP2 NM_152381.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272

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]

XIRP2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1069541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIRP2	NM_152381.6	c.9589A>T	p.Ile3197Phe	missense_variant	9/11	ENST00000409195.6	NP_689594.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XIRP2	ENST00000409195.6	c.9589A>T	p.Ile3197Phe	missense_variant	9/11	5	NM_152381.6	ENSP00000386840.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.0
DANN	Benign	0.90
DEOGEN2	Benign	0.082	.;T;.;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.67	T;T;T;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	.;M;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N;.;N;.
REVEL	Benign	0.058
Sift	Uncertain	0.0050	D;.;D;.
Sift4G	Uncertain	0.031	.;.;.;D
Polyphen		0.61, 0.73	.;P;P;.
Vest4		0.17
MutPred		0.21		.;Loss of methylation at K3019 (P = 0.0898);.;.;
MVP		0.014
MPC		0.056
ClinPred		0.15	T
GERP RS		-4.1
Varity_R		0.035
gMVP		0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs3749004; hg19: chr2-168107491;