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2-186636125-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002210.5(ITGAV):c.675C>T(p.Tyr225=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000532 in 1,612,944 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00032 ( 1 hom. )

Consequence

ITGAV
NM_002210.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0950
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-186636125-C-T is Benign according to our data. Variant chr2-186636125-C-T is described in ClinVar as [Benign]. Clinvar id is 787778.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.095 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 376 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ITGAVNM_002210.5 linkuse as main transcriptc.675C>T p.Tyr225= synonymous_variant 7/30 ENST00000261023.8
ITGAVNM_001145000.3 linkuse as main transcriptc.567C>T p.Tyr189= synonymous_variant 5/28
ITGAVNM_001144999.3 linkuse as main transcriptc.537C>T p.Tyr179= synonymous_variant 7/30
ITGAVXM_047444225.1 linkuse as main transcriptc.-169C>T 5_prime_UTR_variant 3/26

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ITGAVENST00000261023.8 linkuse as main transcriptc.675C>T p.Tyr225= synonymous_variant 7/301 NM_002210.5 P2P06756-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00247
AC:
376
AN:
152004
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00829
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00125
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.000958
GnomAD3 exomes
AF:
0.000705
AC:
177
AN:
250930
Hom.:
0
AF XY:
0.000479
AC XY:
65
AN XY:
135632
show subpopulations
Gnomad AFR exome
AF:
0.00844
Gnomad AMR exome
AF:
0.000696
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000123
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000324
AC:
474
AN:
1460822
Hom.:
1
Cov.:
30
AF XY:
0.000275
AC XY:
200
AN XY:
726750
show subpopulations
Gnomad4 AFR exome
AF:
0.00882
Gnomad4 AMR exome
AF:
0.000716
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000855
Gnomad4 OTH exome
AF:
0.000729
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00252
AC:
384
AN:
152122
Hom.:
3
Cov.:
32
AF XY:
0.00249
AC XY:
185
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.00846
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.000948
Alfa
AF:
0.00110
Hom.:
0
Bravo
AF:
0.00301
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.0000546
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 27, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
11
Dann
Benign
0.34
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs149545302; hg19: chr2-187500852; COSMIC: COSV99655439; API