chr5-52989814-G-GCACACA

Variant names:

• chr5-52989814-G-GCACACA
• rs35389760
• NM_002203.4:c.64+299_64+304dupCACACA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_002203.4(ITGA2):​c.64+299_64+304dupCACACA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.017 (26 hom., cov: 0)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 1 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.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0175 (2553/145904) while in subpopulation SAS AF = 0.0394 (181/4596). AF 95% confidence interval is 0.0347. There are 26 homozygotes in GnomAd4. There are 1274 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2553 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.64+299_64+304dupCACACA		intron	N/A	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.181+299_181+304dupCACACA		intron	N/A
	ITGA2	NR_073104.2		n.181+299_181+304dupCACACA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.64+282_64+283insCACACA		intron	N/A	ENSP00000296585.5	P17301
	ITGA2	ENST00000509814.5	TSL:1	n.64+282_64+283insCACACA		intron	N/A	ENSP00000424397.1	E7EMF1
	ITGA2	ENST00000509960.5	TSL:1	n.64+282_64+283insCACACA		intron	N/A	ENSP00000424642.1	E9PB77

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2536 AN: 145794 Hom.: 25 Cov.: 0

Gnomad AFR AF: 0.0251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0310

Gnomad EAS AF: 0.00725

Gnomad SAS AF: 0.0393

Gnomad FIN AF: 0.0187

Gnomad MID AF: 0.00345

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0162

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0175 AC: 2553 AN: 145904 Hom.: 26 Cov.: 0 AF XY: 0.0180 AC XY: 1274 AN XY: 70940

African (AFR) AF: 0.0255 AC: 1025 AN: 40258

American (AMR) AF: 0.0124 AC: 181 AN: 14634

Ashkenazi Jewish (ASJ) AF: 0.0310 AC: 101 AN: 3256

East Asian (EAS) AF: 0.00747 AC: 37 AN: 4956

South Asian (SAS) AF: 0.0394 AC: 181 AN: 4596

European-Finnish (FIN) AF: 0.0187 AC: 180 AN: 9630

Middle Eastern (MID) AF: 0.00370 AC: 1 AN: 270

European-Non Finnish (NFE) AF: 0.0124 AC: 815 AN: 65466

Other (OTH) AF: 0.0161 AC: 32 AN: 1992

Alfa AF: 0.0168 Hom.: 338

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.060
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs35389760; hg19: chr5-52285644;