2-186622359-G-T

Variant names:

• chr2-186622359-G-T
• NM_002210.5:c.337G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002210.5(ITGAV):​c.337G>T​(p.Asp113Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGAV NM_002210.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.48
• Publications: 0 publications found

Genes affected

ITGAV (HGNC:6150): (integrin subunit alpha V) The product of this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha subunit and a beta subunit that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha V subunit. This subunit associates with beta 1, beta 3, beta 5, beta 6 and beta 8 subunits. The heterodimer consisting of alpha V and beta 3 subunits is also known as the vitronectin receptor. This integrin may regulate angiogenesis and cancer progression. Alternative splicing results in multiple transcript variants. Note that the integrin alpha 5 and integrin alpha V subunits are encoded by distinct genes. [provided by RefSeq, Oct 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.337G>T	p.Asp113Tyr	missense_variant	Exon 3 of 30	ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.337G>T	p.Asp113Tyr	missense_variant	Exon 3 of 28		NP_001138472.2
ITGAV	NM_001144999.3	c.199G>T	p.Asp67Tyr	missense_variant	Exon 3 of 30		NP_001138471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.337G>T	p.Asp113Tyr	missense_variant	Exon 3 of 30	1	NM_002210.5	ENSP00000261023.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.337G>T (p.D113Y) alteration is located in exon 3 (coding exon 3) of the ITGAV gene. This alteration results from a G to T substitution at nucleotide position 337, causing the aspartic acid (D) at amino acid position 113 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.36	T;.;.
Eigen	Benign	0.065
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.7	L;L;.
PhyloP100		2.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Uncertain	0.43
Sift	Benign	0.13	T;T;T
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		0.86	P;B;.
Vest4		0.69
MutPred		0.42		Loss of disorder (P = 0.0306);Loss of disorder (P = 0.0306);.;
MVP		0.97
MPC		0.53
ClinPred		0.84	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.54
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr2-187487086;