5-52989814-GCACACACACACA-GCACACACACACACACACACACACA

Variant names:

• chr5-52989814-G-GCACACACACACA
• rs35389760
• NM_002203.4:c.64+293_64+304dupCACACACACACA

Variant summary

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

The NM_002203.4(ITGA2):​c.64+293_64+304dupCACACACACACA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.012 (18 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 nfe. GnomAd4 allele frequency = 0.0125 (1817/145920) while in subpopulation NFE AF = 0.0174 (1137/65456). AF 95% confidence interval is 0.0165. There are 18 homozygotes in GnomAd4. There are 880 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1817 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+293_64+304dupCACACACACACA		intron	N/A	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.181+293_181+304dupCACACACACACA		intron	N/A
	ITGA2	NR_073104.2		n.181+293_181+304dupCACACACACACA		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+283insCACACACACACA		intron	N/A	ENSP00000296585.5	P17301
	ITGA2	ENST00000509814.5	TSL:1	n.64+282_64+283insCACACACACACA		intron	N/A	ENSP00000424397.1	E7EMF1
	ITGA2	ENST00000509960.5	TSL:1	n.64+282_64+283insCACACACACACA		intron	N/A	ENSP00000424642.1	E9PB77

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1818 AN: 145810 Hom.: 18 Cov.: 0

Gnomad AFR AF: 0.00319

Gnomad AMI AF: 0.00946

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0406

Gnomad EAS AF: 0.00282

Gnomad SAS AF: 0.00585

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0142

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

GnomAD4 genome AF: 0.0125 AC: 1817 AN: 145920 Hom.: 18 Cov.: 0 AF XY: 0.0124 AC XY: 880 AN XY: 70956

African (AFR) AF: 0.00318 AC: 128 AN: 40280

American (AMR) AF: 0.0120 AC: 176 AN: 14628

Ashkenazi Jewish (ASJ) AF: 0.0406 AC: 132 AN: 3254

East Asian (EAS) AF: 0.00262 AC: 13 AN: 4956

South Asian (SAS) AF: 0.00586 AC: 27 AN: 4606

European-Finnish (FIN) AF: 0.0174 AC: 168 AN: 9630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.0174 AC: 1137 AN: 65456

Other (OTH) AF: 0.0140 AC: 28 AN: 1994

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;