Genetic Variant ITGAV:p.Met64Val (chr2-186602025-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002210.5(ITGAV):c.190A>G(p.Met64Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ITGAV
NM_002210.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.09

Publications

0 publications found

Variant links:

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]

ITGAV links:

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ACMG classification

Classification was made for transcript

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=0.170313).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002210.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGAV	NM_002210.5	MANE Select	c.190A>G	p.Met64Val	missense	Exon 2 of 30	NP_002201.2	P06756-1
ITGAV	NM_001145000.3		c.190A>G	p.Met64Val	missense	Exon 2 of 28	NP_001138472.2	P06756-2
ITGAV	NM_001144999.3		c.52A>G	p.Met18Val	missense	Exon 2 of 30	NP_001138471.2	P06756-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITGAV	ENST00000261023.8	TSL:1 MANE Select	c.190A>G	p.Met64Val	missense	Exon 2 of 30	ENSP00000261023.3	P06756-1
ITGAV	ENST00000374907.7	TSL:1	c.190A>G	p.Met64Val	missense	Exon 2 of 28	ENSP00000364042.3	P06756-2
ITGAV	ENST00000925193.1		c.190A>G	p.Met64Val	missense	Exon 2 of 30	ENSP00000595252.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000406

AC:

AN:

246262

AF XY:

0.00000752

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Benign

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.14

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.76

M_CAP

Benign

0.032

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.085

PhyloP100

2.1

PrimateAI

Uncertain

0.74

PROVEAN

Benign

0.57

REVEL

Uncertain

0.44

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.17

MutPred

0.42

Loss of methylation at R63 (P = 0.1889)

MVP

0.84

MPC

0.18

ClinPred

0.052

GERP RS

5.2

Varity_R

0.32

gMVP

0.37

Mutation Taster

=76/24

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over