rs3212385

Variant names:

• chr5-52989345-G-A
• rs3212385
• ENST00000860895.1:c.-124G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000860895.1(ITGA2):​c.-124G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,004,716 control chromosomes in the GnomAD database, including 1,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (643 hom., cov: 33)
  • Exomes 𝑓: 0.0058 (375 hom.)
• Consequence: ITGA2 ENST00000860895.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.21
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-52989345-G-A is Benign according to our data. Variant chr5-52989345-G-A is described in ClinVar as Benign. ClinVar VariationId is 353728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000860895.1. 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+745C>T		intron	N/A
	ITGA2	NM_002203.4	MANE Select	c.-124G>A		upstream_gene	N/A	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.-7G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000860895.1		c.-124G>A		5_prime_UTR	Exon 1 of 30	ENSP00000530954.1
	ITGA2	ENST00000503810.6	TSL:5	n.-124G>A		non_coding_transcript_exon	Exon 1 of 29	ENSP00000426489.1	D6RG08
	ITGA2-AS1	ENST00000765995.1		n.428C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 7526 AN: 152212 Hom.: 642 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.00576 AC: 4908 AN: 852388 Hom.: 375 Cov.: 12 AF XY: 0.00488 AC XY: 2162 AN XY: 443292

African (AFR) AF: 0.176 AC: 3835 AN: 21790

American (AMR) AF: 0.00866 AC: 321 AN: 37088

Ashkenazi Jewish (ASJ) AF: 0.000138 AC: 3 AN: 21720

East Asian (EAS) AF: 0.00 AC: 0 AN: 35244

South Asian (SAS) AF: 0.000425 AC: 30 AN: 70588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50714

Middle Eastern (MID) AF: 0.00950 AC: 44 AN: 4634

European-Non Finnish (NFE) AF: 0.000310 AC: 177 AN: 570476

Other (OTH) AF: 0.0124 AC: 498 AN: 40134

GnomAD4 genome AF: 0.0495 AC: 7533 AN: 152328 Hom.: 643 Cov.: 33 AF XY: 0.0467 AC XY: 3480 AN XY: 74490

African (AFR) AF: 0.172 AC: 7164 AN: 41552

American (AMR) AF: 0.0161 AC: 247 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68028

Other (OTH) AF: 0.0340 AC: 72 AN: 2116

Alfa AF: 0.0278 Hom.: 58

Bravo AF: 0.0565

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Platelet-type bleeding disorder 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.89
PhyloP100		2.2
PromoterAI		-0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=297/3	polymorphism (auto)

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: rs3212385; hg19: chr5-52285175;