chr6-32746090-C-T

Variant names:

• chr6-32746090-C-T
• rs9276435
• NM_020056.5:c.613+18C>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.613+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,603,848 control chromosomes in the GnomAD database, including 18,921 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 0.12 (778 hom., cov: 35)
  • Exomes 𝑓: 0.17 (18143 hom.)
• Consequence: HLA-DQA2 NM_020056.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 31 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 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.613+18C>T		intron	N/A	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.613+18C>T		intron	N/A	ENSP00000364076.3

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18844 AN: 151530 Hom.: 777 Cov.: 35

Gnomad AFR AF: 0.0561

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0247

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.120

GnomAD2 exomes AF: 0.133 AC: 32790 AN: 245916 AF XY: 0.137

Gnomad AFR exome AF: 0.0536

Gnomad AMR exome AF: 0.0639

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.0211

Gnomad FIN exome AF: 0.183

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.169 AC: 245381 AN: 1452198 Hom.: 18143 Cov.: 66 AF XY: 0.168 AC XY: 121184 AN XY: 722554

African (AFR) AF: 0.0518 AC: 1731 AN: 33424

American (AMR) AF: 0.0666 AC: 2970 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3543 AN: 26042

East Asian (EAS) AF: 0.0158 AC: 625 AN: 39626

South Asian (SAS) AF: 0.120 AC: 10326 AN: 86056

European-Finnish (FIN) AF: 0.186 AC: 9715 AN: 52248

Middle Eastern (MID) AF: 0.124 AC: 710 AN: 5742

European-Non Finnish (NFE) AF: 0.187 AC: 206146 AN: 1104334

Other (OTH) AF: 0.160 AC: 9615 AN: 60160

GnomAD4 genome AF: 0.124 AC: 18837 AN: 151650 Hom.: 778 Cov.: 35 AF XY: 0.123 AC XY: 9108 AN XY: 74158

African (AFR) AF: 0.0560 AC: 2326 AN: 41514

American (AMR) AF: 0.108 AC: 1644 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 462 AN: 3464

East Asian (EAS) AF: 0.0247 AC: 128 AN: 5176

South Asian (SAS) AF: 0.0938 AC: 451 AN: 4808

European-Finnish (FIN) AF: 0.176 AC: 1858 AN: 10530

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11607 AN: 67588

Other (OTH) AF: 0.119 AC: 249 AN: 2098

Alfa AF: 0.154 Hom.: 3722

Asia WGS AF: 0.0700 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.9
DANN	Benign	0.84
PhyloP100		-1.4
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: rs9276435; hg19: chr6-32713867; COSMIC: COSV66565222; COSMIC: COSV66565222;