chr2-186668641-C-A

Variant names:

• chr2-186668641-C-A
• rs11685758
• NM_002210.5:c.2434-121C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002210.5(ITGAV):​c.2434-121C>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597
• Publications: 11 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]

ENSG00000227227 (HGNC:41242):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAV	NM_002210.5	MANE Select	c.2434-121C>A		intron	N/A	NP_002201.2
	ITGAV	NM_001145000.3		c.2326-121C>A		intron	N/A	NP_001138472.2
	ITGAV	NM_001144999.3		c.2296-121C>A		intron	N/A	NP_001138471.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAV	ENST00000261023.8	TSL:1 MANE Select	c.2434-121C>A		intron	N/A	ENSP00000261023.3
	ITGAV	ENST00000374907.7	TSL:1	c.2326-121C>A		intron	N/A	ENSP00000364042.3
	ITGAV	ENST00000496854.2	TSL:3	n.118C>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 624858 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 333216

African (AFR) AF: 0.00 AC: 0 AN: 15036

American (AMR) AF: 0.00 AC: 0 AN: 21880

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17740

East Asian (EAS) AF: 0.00 AC: 0 AN: 32956

South Asian (SAS) AF: 0.00 AC: 0 AN: 56284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3992

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 396446

Other (OTH) AF: 0.00 AC: 0 AN: 31912

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.51
PhyloP100		0.60
PromoterAI		0.0085	Neutral

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

Other links and lift over

dbSNP: rs11685758; hg19: chr2-187533368;