6-32641437-G-A

Variant names:

• chr6-32641437-G-A
• NM_002122.5:c.210G>A
• HLA-DQA1 p.Arg70Arg

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_002122.5(HLA-DQA1):​c.210G>A​(p.Arg70Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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: not found (cov: 13)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA1 NM_002122.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• 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]

HLA-DQA1-AS1 (HGNC:56667): (HLA-DQA1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.007).
• BP7: Synonymous conserved (PhyloP=-0.084 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002122.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA1	NM_002122.5	MANE Select	c.210G>A	p.Arg70Arg	synonymous	Exon 2 of 5	NP_002113.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA1	ENST00000343139.11	TSL:6 MANE Select	c.210G>A	p.Arg70Arg	synonymous	Exon 2 of 5	ENSP00000339398.5	P01909
	HLA-DQA1	ENST00000374949.2	TSL:6	c.210G>A	p.Arg70Arg	synonymous	Exon 2 of 4	ENSP00000364087.2	P01909
	HLA-DQA1	ENST00000395363.5	TSL:6	c.210G>A	p.Arg70Arg	synonymous	Exon 2 of 5	ENSP00000378767.1	P01909

Frequencies

GnomAD3 genomes Cov.: 13

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 934424 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 470010

African (AFR) AF: 0.00 AC: 0 AN: 24328

American (AMR) AF: 0.00 AC: 0 AN: 21342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15780

East Asian (EAS) AF: 0.00 AC: 0 AN: 26546

South Asian (SAS) AF: 0.00 AC: 0 AN: 64884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3388

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 699764

Other (OTH) AF: 0.00 AC: 0 AN: 39304

GnomAD4 genome Cov.: 13

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.46
PhyloP100		-0.084
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-32609214;