chr6-32747006-A-T

Variant names:

• chr6-32747006-A-T
• rs9276440
• NM_020056.5:c.*445A>T

Variant summary

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

The NM_020056.5(HLA-DQA2):​c.*445A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 256,948 control chromosomes in the GnomAD database, including 49,145 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 0.62 (29279 hom., cov: 29)
  • Exomes 𝑓: 0.60 (19866 hom.)
• Consequence: HLA-DQA2 NM_020056.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 14 publications found

Genes affected

HLA-DQA2 (HGNC:4943): (major histocompatibility complex, class II, DQ alpha 2) This gene belongs to the HLA class II alpha chain family. The encoded protein forms a heterodimer with a class II beta chain. It is located in intracellular vesicles and plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (B lymphocytes, dendritic cells, macrophages) and are used to present antigenic peptides on the cell surface to be recognized by CD4 T-cells. [provided by RefSeq, Jun 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020056.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA2	NM_020056.5	MANE Select	c.*445A>T		3_prime_UTR	Exon 5 of 5	NP_064440.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA2	ENST00000374940.4	TSL:6 MANE Select	c.*445A>T		3_prime_UTR	Exon 5 of 5	ENSP00000364076.3

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93466 AN: 151582 Hom.: 29242 Cov.: 29

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.671

GnomAD4 exome AF: 0.603 AC: 63442 AN: 105246 Hom.: 19866 Cov.: 0 AF XY: 0.614 AC XY: 34075 AN XY: 55516

African (AFR) AF: 0.631 AC: 2160 AN: 3424

American (AMR) AF: 0.702 AC: 3973 AN: 5656

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 1534 AN: 2380

East Asian (EAS) AF: 0.817 AC: 4677 AN: 5726

South Asian (SAS) AF: 0.680 AC: 10155 AN: 14928

European-Finnish (FIN) AF: 0.543 AC: 2265 AN: 4172

Middle Eastern (MID) AF: 0.668 AC: 250 AN: 374

European-Non Finnish (NFE) AF: 0.558 AC: 35214 AN: 63088

Other (OTH) AF: 0.585 AC: 3214 AN: 5498

GnomAD4 genome AF: 0.617 AC: 93562 AN: 151702 Hom.: 29279 Cov.: 29 AF XY: 0.622 AC XY: 46125 AN XY: 74128

African (AFR) AF: 0.644 AC: 26596 AN: 41312

American (AMR) AF: 0.684 AC: 10428 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2226 AN: 3468

East Asian (EAS) AF: 0.813 AC: 4197 AN: 5160

South Asian (SAS) AF: 0.697 AC: 3352 AN: 4810

European-Finnish (FIN) AF: 0.582 AC: 6110 AN: 10494

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38365 AN: 67896

Other (OTH) AF: 0.676 AC: 1424 AN: 2106

Alfa AF: 0.449 Hom.: 1164

Bravo AF: 0.630

Asia WGS AF: 0.725 AC: 2517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.0
DANN	Benign	0.42
PhyloP100		0.019
Mutation Taster		=100/0	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: rs9276440; hg19: chr6-32714783;