5-52989370-G-C

Variant names:

• chr5-52989370-G-C
• rs886060656
• NM_002203.4:c.-99G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002203.4(ITGA2):​c.-99G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000339 in 1,120,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: ITGA2 NM_002203.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.253
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BS2: High AC in GnomAdExome4 at 38 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002203.4. 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	NM_002203.4	MANE Select	c.-99G>C		5_prime_UTR	Exon 1 of 30	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.19G>C		non_coding_transcript_exon	Exon 1 of 29
	ITGA2	NR_073104.2		n.19G>C		non_coding_transcript_exon	Exon 1 of 29

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.-99G>C		5_prime_UTR	Exon 1 of 30	ENSP00000296585.5	P17301
	ITGA2	ENST00000860895.1		c.-99G>C		5_prime_UTR	Exon 1 of 30	ENSP00000530954.1
	ITGA2	ENST00000503810.6	TSL:5	n.-99G>C		non_coding_transcript_exon	Exon 1 of 29	ENSP00000426489.1	D6RG08

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000339 AC: 38 AN: 1120882 Hom.: 0 Cov.: 15 AF XY: 0.0000402 AC XY: 23 AN XY: 571552

African (AFR) AF: 0.00 AC: 0 AN: 26922

American (AMR) AF: 0.0000237 AC: 1 AN: 42180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23710

East Asian (EAS) AF: 0.00 AC: 0 AN: 37728

South Asian (SAS) AF: 0.0000638 AC: 5 AN: 78344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52442

Middle Eastern (MID) AF: 0.000976 AC: 5 AN: 5122

European-Non Finnish (NFE) AF: 0.0000323 AC: 26 AN: 805270

Other (OTH) AF: 0.0000203 AC: 1 AN: 49164

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Platelet-type bleeding disorder 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.7
DANN	Benign	0.74
PhyloP100		0.25
PromoterAI		-0.15	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: rs886060656; hg19: chr5-52285200;