6-33091892-G-T

Variant names:

• chr6-33091892-G-T
• rs2281390
• ENST00000433582.1:n.594C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000433582.1(HLA-DPA2):​n.594C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,840 control chromosomes in the GnomAD database, including 2,825 homozygotes. 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: 𝑓 0.18 (2808 hom., cov: 32)
  • Exomes 𝑓: 0.21 (17 hom.)
• Consequence: HLA-DPA2 ENST00000433582.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.667
• Publications: 35 publications found

Genes affected

HLA-DPA2 (HGNC:4939): (major histocompatibility complex, class II, DP alpha 2 (pseudogene))

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DPA2		n.33091892G>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DPA2	ENST00000433582.1	n.594C>A		non_coding_transcript_exon_variant	Exon 4 of 4	6

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27191 AN: 152080 Hom.: 2804 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.0578

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.207 AC: 133 AN: 642 Hom.: 17 Cov.: 0 AF XY: 0.198 AC XY: 84 AN XY: 424

African (AFR) AF: 0.125 AC: 1 AN: 8

American (AMR) AF: 0.833 AC: 5 AN: 6

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.229 AC: 78 AN: 340

Middle Eastern (MID) AF: 0.333 AC: 2 AN: 6

European-Non Finnish (NFE) AF: 0.174 AC: 45 AN: 258

Other (OTH) AF: 0.0909 AC: 2 AN: 22

GnomAD4 genome AF: 0.179 AC: 27214 AN: 152198 Hom.: 2808 Cov.: 32 AF XY: 0.183 AC XY: 13619 AN XY: 74396

African (AFR) AF: 0.131 AC: 5461 AN: 41536

American (AMR) AF: 0.308 AC: 4710 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3466

East Asian (EAS) AF: 0.0586 AC: 303 AN: 5174

South Asian (SAS) AF: 0.140 AC: 674 AN: 4828

European-Finnish (FIN) AF: 0.248 AC: 2623 AN: 10582

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12065 AN: 67998

Other (OTH) AF: 0.183 AC: 388 AN: 2116

Alfa AF: 0.179 Hom.: 11328

Bravo AF: 0.186

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.67
PhyloP100		0.67

Splicing

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

Other links and lift over

dbSNP: rs2281390; hg19: chr6-33059669;