chr6-32641426-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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 (★).

• 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
• Publications: 1 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 -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 VariationId is 3257709.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 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.199A>G	p.Thr67Ala	missense	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.199A>G	p.Thr67Ala	missense	Exon 2 of 5	ENSP00000339398.5	P01909
	HLA-DQA1	ENST00000374949.2	TSL:6	c.199A>G	p.Thr67Ala	missense	Exon 2 of 4	ENSP00000364087.2	P01909
	HLA-DQA1	ENST00000395363.5	TSL:6	c.199A>G	p.Thr67Ala	missense	Exon 2 of 5	ENSP00000378767.1	P01909

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

GnomAD2 exomes AF: 0.000122 AC: 24 AN: 196278 AF XY: 0.000168

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 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

African (AFR) AF: 0.0000790 AC: 2 AN: 25326

American (AMR) AF: 0.0000878 AC: 2 AN: 22780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16664

East Asian (EAS) AF: 0.00 AC: 0 AN: 27478

South Asian (SAS) AF: 0.000103 AC: 7 AN: 68056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3688

European-Non Finnish (NFE) AF: 0.000193 AC: 141 AN: 729200

Other (OTH) AF: 0.000122 AC: 5 AN: 41140

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

African (AFR) AF: 0.0000368 AC: 1 AN: 27208

American (AMR) AF: 0.00 AC: 0 AN: 7682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2016

East Asian (EAS) AF: 0.00 AC: 0 AN: 2908

South Asian (SAS) AF: 0.00 AC: 0 AN: 3088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 150

European-Non Finnish (NFE) AF: 0.000163 AC: 7 AN: 43036

Other (OTH) AF: 0.00 AC: 0 AN: 1210

Alfa AF: 0.000106 Hom.: 1

ExAC AF: 0.000108 AC: 13

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
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
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.92	T
PhyloP100		3.8
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.20
Sift	Benign	0.13	T
Sift4G	Benign	0.17	T
Vest4		0.69
MVP		0.47
MPC		1.9
ClinPred		0.36	T
GERP RS		3.8
gMVP		0.35
Mutation Taster		=97/3	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

Other links and lift over

dbSNP: rs41543221; hg19: chr6-32609203;