rs1142331

chr6-32641477-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002122.5(HLA-DQA1):c.250G>T(p.Gly84Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (36 hom., cov: 13)
  • Exomes 𝑓: 0.0052 (2280 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA1 NM_002122.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.47

Genes affected

HLA-DQA1 (HGNC:4942): (major histocompatibility complex, class II, DQ alpha 1) HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B Lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa. It is encoded by 5 exons; exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011225879).
• BS2: High Homozygotes in GnomAd at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DQA1	NM_002122.5	c.250G>T	p.Gly84Cys	missense_variant	2/5	ENST00000343139.11
HLA-DQA1	XM_006715079.5	c.250G>T	p.Gly84Cys	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.250G>T	p.Gly84Cys	missense_variant	2/5		NM_002122.5	P1

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1009 AN: 81226 Hom.: 35 Cov.: 13

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.00800

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00714

Gnomad SAS AF: 0.00664

Gnomad FIN AF: 0.00720

Gnomad MID AF: 0.00794

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0125

GnomAD3 exomes AF: 0.0753 AC: 10718 AN: 142246 Hom.: 4472 AF XY: 0.0717 AC XY: 5568 AN XY: 77616

Gnomad AFR exome AF: 0.0967

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.0561

Gnomad EAS exome AF: 0.0775

Gnomad SAS exome AF: 0.0431

Gnomad FIN exome AF: 0.0628

Gnomad NFE exome AF: 0.0803

Gnomad OTH exome AF: 0.0511

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00523 AC: 4848 AN: 926826 Hom.: 2280 Cov.: 24 AF XY: 0.00605 AC XY: 2809 AN XY: 464428

Gnomad4 AFR exome AF: 0.00461

Gnomad4 AMR exome AF: 0.0223

Gnomad4 ASJ exome AF: 0.00770

Gnomad4 EAS exome AF: 0.00487

Gnomad4 SAS exome AF: 0.0129

Gnomad4 FIN exome AF: 0.00645

Gnomad4 NFE exome AF: 0.00394

Gnomad4 OTH exome AF: 0.00587

GnomAD4 genome AF: 0.0124 AC: 1010 AN: 81322 Hom.: 36 Cov.: 13 AF XY: 0.0116 AC XY: 457 AN XY: 39446

Gnomad4 AFR AF: 0.0128

Gnomad4 AMR AF: 0.0138

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.00677

Gnomad4 SAS AF: 0.00663

Gnomad4 FIN AF: 0.00720

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.182 Hom.: 747

ExAC AF: 0.306 AC: 33558

Asia WGS AF: 0.443 AC: 1523 AN: 3436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	18
Dann	Benign	0.94
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.26	N
MetaRNN	Benign	0.011	T;T;T;T
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-6.8	D;D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Vest4		0.23
MPC		1.7
ClinPred		0.057	T
GERP RS		2.1
gMVP		0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1142331; hg19: chr6-32609254; COSMIC: COSV58237257; COSMIC: COSV58237257;