6-32641426-A-G

Variant names:

• chr6-32641426-A-G
• rs41543221
• NM_002122.5:c.199A>G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The NM_002122.5(HLA-DQA1):​c.199A>G​(p.Thr67Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000154 in 1,070,518 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.000084 (2 hom., cov: 15)
  • Exomes 𝑓: 0.00016 (52 hom.)
• Consequence: HLA-DQA1 NM_002122.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.77

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

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.40534523).
• BP6: Variant 6-32641426-A-G is Benign according to our data. Variant chr6-32641426-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3257709.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.199A>G	p.Thr67Ala	missense_variant	Exon 2 of 5	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5	c.199A>G	p.Thr67Ala	missense_variant	Exon 2 of 4		XP_006715142.1
HLA-DQA1-AS1	XR_007059544.1	n.-116T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.199A>G	p.Thr67Ala	missense_variant	Exon 2 of 5	6	NM_002122.5	ENSP00000339398.5

Frequencies

GnomAD3 genomes AF: 0.0000844 AC: 8 AN: 94764 Hom.: 2 Cov.: 15

Gnomad AFR AF: 0.0000368

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000163

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000122 AC: 24 AN: 196278 Hom.: 6 AF XY: 0.000168 AC XY: 18 AN XY: 107314

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000158

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000183

Gnomad OTH exome AF: 0.000642

GnomAD4 exome AF: 0.000161 AC: 157 AN: 975754 Hom.: 52 Cov.: 27 AF XY: 0.000189 AC XY: 93 AN XY: 491690

Gnomad4 AFR exome AF: 0.0000790

Gnomad4 AMR exome AF: 0.0000878

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000103

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000193

Gnomad4 OTH exome AF: 0.000122

GnomAD4 genome AF: 0.0000844 AC: 8 AN: 94764 Hom.: 2 Cov.: 15 AF XY: 0.000109 AC XY: 5 AN XY: 46082

Gnomad4 AFR AF: 0.0000368

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000163

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000106 Hom.: 1

ExAC AF: 0.000108 AC: 13

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HLA-DQA1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	.;.;T;.
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.73	.;.;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.41	T;T;T;T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.3	D;D;D;D
REVEL	Benign	0.20
Sift	Benign	0.13	T;T;T;T
Sift4G	Benign	0.17	T;T;T;T
Vest4		0.69
MVP		0.47
MPC		1.9
ClinPred		0.36	T
GERP RS		3.8
gMVP		0.35

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: rs41543221; hg19: chr6-32609203;