2-167250981-A-T

Variant names:

• chr2-167250981-A-T
• rs3749004
• NM_152381.6:c.9589A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• Publications: 20 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: Uncertain_significance. The variant received 0 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIRP2	NM_152381.6	MANE Select	c.9589A>T	p.Ile3197Phe	missense	Exon 9 of 11	NP_689594.4
	XIRP2	NM_001199144.2		c.8923A>T	p.Ile2975Phe	missense	Exon 7 of 9	NP_001186073.1	A4UGR9-2
	XIRP2	NM_001199143.2		c.1276-3051A>T		intron	N/A	NP_001186072.1	A4UGR9-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XIRP2	ENST00000409195.6	TSL:5 MANE Select	c.9589A>T	p.Ile3197Phe	missense	Exon 9 of 11	ENSP00000386840.2	A4UGR9-8
	XIRP2	ENST00000409273.6	TSL:1	c.8923A>T	p.Ile2975Phe	missense	Exon 7 of 9	ENSP00000387255.1	A4UGR9-2
	XIRP2	ENST00000409728.5	TSL:1	c.1276-3051A>T		intron	N/A	ENSP00000386619.1	A4UGR9-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.27
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.058
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.031	D
Polyphen		0.61	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
Mutation Taster		=98/2	polymorphism

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: rs3749004; hg19: chr2-168107491;