chr6-32641437-G-T

Variant names:

• chr6-32641437-G-T
• rs3207984
• NM_002122.5:c.210G>T
• HLA-DQA1 p.Arg70Arg

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_002122.5(HLA-DQA1):​c.210G>T​(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: 𝑓 0.029 (179 hom., cov: 13)
  • Exomes 𝑓: 0.023 (7906 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA1 NM_002122.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 9 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.007).
• BP7: Synonymous conserved (PhyloP=-0.084 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 179 AR gene

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>T	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>T	p.Arg70Arg	synonymous	Exon 2 of 5	ENSP00000339398.5	P01909
	HLA-DQA1	ENST00000374949.2	TSL:6	c.210G>T	p.Arg70Arg	synonymous	Exon 2 of 4	ENSP00000364087.2	P01909
	HLA-DQA1	ENST00000395363.5	TSL:6	c.210G>T	p.Arg70Arg	synonymous	Exon 2 of 5	ENSP00000378767.1	P01909

Frequencies

GnomAD3 genomes AF: 0.0286 AC: 2240 AN: 78450 Hom.: 179 Cov.: 13

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.0200

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.0381

Gnomad EAS AF: 0.0165

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.0139

Gnomad MID AF: 0.0526

Gnomad NFE AF: 0.0343

Gnomad OTH AF: 0.0248

GnomAD2 exomes AF: 0.161 AC: 27720 AN: 172570 AF XY: 0.160

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.135

Gnomad EAS exome AF: 0.141

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.168

Gnomad OTH exome AF: 0.119

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0230 AC: 21001 AN: 912042 Hom.: 7906 Cov.: 27 AF XY: 0.0270 AC XY: 12370 AN XY: 457706

African (AFR) AF: 0.0226 AC: 535 AN: 23718

American (AMR) AF: 0.122 AC: 2502 AN: 20546

Ashkenazi Jewish (ASJ) AF: 0.0397 AC: 608 AN: 15302

East Asian (EAS) AF: 0.0279 AC: 721 AN: 25828

South Asian (SAS) AF: 0.0517 AC: 3260 AN: 63006

European-Finnish (FIN) AF: 0.0330 AC: 1206 AN: 36518

Middle Eastern (MID) AF: 0.0695 AC: 218 AN: 3136

European-Non Finnish (NFE) AF: 0.0162 AC: 11137 AN: 685612

Other (OTH) AF: 0.0212 AC: 814 AN: 38376

GnomAD4 genome AF: 0.0285 AC: 2241 AN: 78524 Hom.: 179 Cov.: 13 AF XY: 0.0278 AC XY: 1061 AN XY: 38204

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0264 AC: 599 AN: 22710

American (AMR) AF: 0.0252 AC: 159 AN: 6322

Ashkenazi Jewish (ASJ) AF: 0.0381 AC: 61 AN: 1602

East Asian (EAS) AF: 0.0162 AC: 41 AN: 2536

South Asian (SAS) AF: 0.0191 AC: 50 AN: 2616

European-Finnish (FIN) AF: 0.0139 AC: 83 AN: 5960

Middle Eastern (MID) AF: 0.0556 AC: 6 AN: 108

European-Non Finnish (NFE) AF: 0.0343 AC: 1207 AN: 35184

Other (OTH) AF: 0.0254 AC: 25 AN: 986

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.104 Hom.: 324

Asia WGS AF: 0.251 AC: 869 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.45
PhyloP100		-0.084
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

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

Other links and lift over

dbSNP: rs3207984; hg19: chr6-32609214; COSMIC: COSV58238919; COSMIC: COSV58238919;