ENST00000503559.1:n.189+874C>T

Variant names:

• chr5-52989216-G-A
• ENST00000503559.1:n.189+874C>T

Variant summary

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

The ENST00000503559.1(ITGA2-AS1):​n.189+874C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 400,628 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: ITGA2-AS1 ENST00000503559.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• Publications: 0 publications found

Genes affected

ITGA2-AS1 (HGNC:40306): (ITGA2 antisense RNA 1)

ITGA2 (HGNC:6137): (integrin subunit alpha 2) This gene encodes the alpha subunit of a transmembrane receptor for collagens and related proteins. The encoded protein forms a heterodimer with a beta subunit and mediates the adhesion of platelets and other cell types to the extracellular matrix. Loss of the encoded protein is associated with bleeding disorder platelet-type 9. Antibodies against this protein are found in several immune disorders, including neonatal alloimmune thrombocytopenia. This gene is located adjacent to a related alpha subunit gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ITGA2 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 9

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

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=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000503559.1. 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
	ITGA2-AS1	NR_186583.1		n.197+874C>T		intron	N/A
	ITGA2	NM_002203.4	MANE Select	c.-253G>A		upstream_gene	N/A	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.-136G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2-AS1	ENST00000503559.1	TSL:5	n.189+874C>T		intron	N/A
	ITGA2-AS1	ENST00000505701.5	TSL:4	n.189+874C>T		intron	N/A
	ITGA2-AS1	ENST00000662246.1		n.75+874C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000250 AC: 1 AN: 400628 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 212454

African (AFR) AF: 0.00 AC: 0 AN: 9888

American (AMR) AF: 0.00 AC: 0 AN: 15548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11898

East Asian (EAS) AF: 0.00 AC: 0 AN: 26846

South Asian (SAS) AF: 0.00 AC: 0 AN: 42784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1774

European-Non Finnish (NFE) AF: 0.00000415 AC: 1 AN: 241084

Other (OTH) AF: 0.00 AC: 0 AN: 23026

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.2
DANN	Uncertain	0.98
PhyloP100		-0.12
PromoterAI		-0.12	Neutral

Splicing

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

Other links and lift over

hg19: chr5-52285046;