rs707963

Positions:

• chr6-32642192-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002122.5(HLA-DQA1):​c.552T>G​(p.Asp184Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 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 0.018 (16 hom., cov: 16)
  • Exomes 𝑓: 0.079 (14160 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA1 NM_002122.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018129051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.552T>G	p.Asp184Glu	missense_variant	3/5	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5	c.552T>G	p.Asp184Glu	missense_variant	3/4		XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.552T>G	p.Asp184Glu	missense_variant	3/5		NM_002122.5	ENSP00000339398	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1571 AN: 89682 Hom.: 17 Cov.: 16 FAILED QC

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.00825

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.0272

Gnomad EAS AF: 0.00886

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.00888

Gnomad MID AF: 0.0303

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0113

GnomAD3 exomes AF: 0.165 AC: 33775 AN: 204164 Hom.: 6483 AF XY: 0.169 AC XY: 18692 AN XY: 110684

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.236

Gnomad EAS exome AF: 0.122

Gnomad SAS exome AF: 0.189

Gnomad FIN exome AF: 0.0964

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.175

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0790 AC: 85290 AN: 1079034 Hom.: 14160 Cov.: 33 AF XY: 0.0834 AC XY: 45110 AN XY: 540736

Gnomad4 AFR exome AF: 0.0589

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.0519

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.0544

Gnomad4 NFE exome AF: 0.0716

Gnomad4 OTH exome AF: 0.0833

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0175 AC: 1573 AN: 89768 Hom.: 16 Cov.: 16 AF XY: 0.0158 AC XY: 693 AN XY: 43800

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.0272

Gnomad4 EAS AF: 0.00922

Gnomad4 SAS AF: 0.0172

Gnomad4 FIN AF: 0.00888

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.0111

Alfa AF: 0.198 Hom.: 762

ESP6500AA AF: 0.128 AC: 387

ESP6500EA AF: 0.155 AC: 838

ExAC AF: 0.202 AC: 23609

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.93
DEOGEN2	Benign	0.00020	.;.;T;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.71	.;.;T;T
MetaRNN	Benign	0.0018	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	0.99	P;P;P;P
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.24	N;N;N;N
REVEL	Benign	0.080
Sift	Benign	0.61	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Vest4		0.088
MutPred		0.45		Gain of solvent accessibility (P = 0.1014);Gain of solvent accessibility (P = 0.1014);Gain of solvent accessibility (P = 0.1014);Gain of solvent accessibility (P = 0.1014);
MPC		0.78
ClinPred		0.0021	T
GERP RS		-0.81
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs707963; hg19: chr6-32609969; COSMIC: COSV58239524; COSMIC: COSV58239524;