NM_002210.5:c.675C>T

Variant names:

• chr2-186636125-C-T
• rs149545302
• NM_002210.5:c.675C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002210.5(ITGAV):​c.675C>T​(p.Tyr225Tyr) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0950
• Publications: 2 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 2-186636125-C-T is Benign according to our data. Variant chr2-186636125-C-T is described in ClinVar as Benign. ClinVar VariationId is 787778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.095 with no splicing effect.
• BS2: High AC in GnomAd4 at 384 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAV	NM_002210.5	MANE Select	c.675C>T	p.Tyr225Tyr	synonymous	Exon 7 of 30	NP_002201.2	P06756-1
	ITGAV	NM_001145000.3		c.567C>T	p.Tyr189Tyr	synonymous	Exon 5 of 28	NP_001138472.2	P06756-2
	ITGAV	NM_001144999.3		c.537C>T	p.Tyr179Tyr	synonymous	Exon 7 of 30	NP_001138471.2	P06756-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAV	ENST00000261023.8	TSL:1 MANE Select	c.675C>T	p.Tyr225Tyr	synonymous	Exon 7 of 30	ENSP00000261023.3	P06756-1
	ITGAV	ENST00000374907.7	TSL:1	c.567C>T	p.Tyr189Tyr	synonymous	Exon 5 of 28	ENSP00000364042.3	P06756-2
	ITGAV	ENST00000925193.1		c.675C>T	p.Tyr225Tyr	synonymous	Exon 7 of 30	ENSP00000595252.1

Frequencies

GnomAD3 genomes AF: 0.00247 AC: 376 AN: 152004 Hom.: 2 Cov.: 32

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

GnomAD2 exomes AF: 0.000705 AC: 177 AN: 250930 AF XY: 0.000479

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 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

African (AFR) AF: 0.00882 AC: 295 AN: 33430

American (AMR) AF: 0.000716 AC: 32 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39564

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.0000855 AC: 95 AN: 1111388

Other (OTH) AF: 0.000729 AC: 44 AN: 60348

GnomAD4 genome AF: 0.00252 AC: 384 AN: 152122 Hom.: 3 Cov.: 32 AF XY: 0.00249 AC XY: 185 AN XY: 74358

African (AFR) AF: 0.00846 AC: 351 AN: 41498

American (AMR) AF: 0.00124 AC: 19 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67996

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00109 Hom.: 0

Bravo AF: 0.00301

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.34
PhyloP100		-0.095
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

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