Genetic Variant ITGAV:p.Arg241Gly (chr2-186636171-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_002210.5(ITGAV):c.721C>G(p.Arg241Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,372 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R241W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ITGAV
NM_002210.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.55

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.721C>G	p.Arg241Gly	missense	Exon 7 of 30	NP_002201.2	P06756-1
ITGAV	NM_001145000.3		c.613C>G	p.Arg205Gly	missense	Exon 5 of 28	NP_001138472.2	P06756-2
ITGAV	NM_001144999.3		c.583C>G	p.Arg195Gly	missense	Exon 7 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.721C>G	p.Arg241Gly	missense	Exon 7 of 30	ENSP00000261023.3	P06756-1
ITGAV	ENST00000374907.7	TSL:1	c.613C>G	p.Arg205Gly	missense	Exon 5 of 28	ENSP00000364042.3	P06756-2
ITGAV	ENST00000925193.1		c.721C>G	p.Arg241Gly	missense	Exon 7 of 30	ENSP00000595252.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460372

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726446

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33416

American (AMR)

AF:

0.00

AC:

AN:

44544

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26096

East Asian (EAS)

AF:

0.00

AC:

AN:

39542

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85922

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111390

Other (OTH)

AF:

0.00

AC:

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.0079

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.68

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

1.5

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.15

Sift

Benign

0.055

Sift4G

Benign

0.19

Polyphen

0.99

Vest4

0.68

MutPred

0.47

Gain of relative solvent accessibility (P = 0.0479)

MVP

0.54

MPC

0.33

ClinPred

0.97

GERP RS

4.7

Varity_R

0.71

gMVP

0.86

Mutation Taster

=67/33

polymorphism

(source)

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

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