rs707963

Variant names:

• chr6-32642192-T-A
• rs707963
• NM_002122.5:c.552T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-32642192-T-A
• chr6-32642192-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002122.5(HLA-DQA1):​c.552T>A​(p.Asp184Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,214,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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: not found (cov: 16)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: HLA-DQA1 NM_002122.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12436509).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.552T>A	p.Asp184Glu	missense_variant	Exon 3 of 5	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5	c.552T>A	p.Asp184Glu	missense_variant	Exon 3 of 4		XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.552T>A	p.Asp184Glu	missense_variant	Exon 3 of 5	6	NM_002122.5	ENSP00000339398.5

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome AF: 0.00000165 AC: 2 AN: 1214458 Hom.: 0 Cov.: 33 AF XY: 0.00000327 AC XY: 2 AN XY: 611258

African (AFR) AF: 0.00 AC: 0 AN: 28682

American (AMR) AF: 0.00 AC: 0 AN: 42034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23310

East Asian (EAS) AF: 0.00 AC: 0 AN: 35840

South Asian (SAS) AF: 0.00 AC: 0 AN: 81148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4630

European-Non Finnish (NFE) AF: 0.00000222 AC: 2 AN: 899018

Other (OTH) AF: 0.00 AC: 0 AN: 51152

GnomAD4 genome Cov.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.92
DEOGEN2	Benign	0.00020	.;.;T;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.71	.;.;T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.95	T
PhyloP100		-1.2
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.24	N;N;N;N
REVEL	Benign	0.081
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);
MVP		0.048
MPC		0.78
ClinPred		0.25	T
GERP RS		-0.81
gMVP		0.66
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs707963; hg19: chr6-32609969;