dbSNP rs768430610: ITGAV:p.Met64Leu (chr2-186602025-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002210.5(ITGAV):c.190A>C(p.Met64Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. M64V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ITGAV
NM_002210.5 missense

Scores

Clinical Significance

Not reported in ClinVar

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32400075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAV	NM_002210.5 link	c.190A>C	p.Met64Leu	missense_variant	Exon 2 of 30	ENST00000261023.8	NP_002201.2	P06756-1L7RXH0
ITGAV	NM_001145000.3 link	c.190A>C	p.Met64Leu	missense_variant	Exon 2 of 28		NP_001138472.2	P06756-2
ITGAV	NM_001144999.3 link	c.52A>C	p.Met18Leu	missense_variant	Exon 2 of 30		NP_001138471.2	P06756-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8 link	c.190A>C	p.Met64Leu	missense_variant	Exon 2 of 30	1	NM_002210.5	ENSP00000261023.3		P06756-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455038

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723554

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33132

American (AMR)

AF:

0.00

AC:

AN:

43544

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25888

East Asian (EAS)

AF:

0.00

AC:

AN:

39560

South Asian (SAS)

AF:

0.00

AC:

AN:

84390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1109402

Other (OTH)

AF:

0.00

AC:

AN:

60114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.030

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.17

T;.;.

Eigen

Benign

-0.062

Eigen_PC

Benign

0.092

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Uncertain

0.13

MutationAssessor

Benign

1.9

L;L;.

PhyloP100

2.1

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.33

N;N;N

REVEL

Uncertain

0.48

Sift

Benign

0.19

T;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.36

MutPred

0.47

Loss of methylation at R63 (P = 0.1403);Loss of methylation at R63 (P = 0.1403);.;

MVP

0.86

MPC

0.17

ClinPred

0.33

GERP RS

5.2

Varity_R

0.34

gMVP

0.36

Mutation Taster

=82/18

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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rs768430610

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over