rs9272863

Variant names:

• chr6-32642953-T-A
• rs9272863
• NM_002122.5:c.*22T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002122.5(HLA-DQA1):​c.*22T>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA1 NM_002122.5 splice_region
• Scores: Splicing: ADA: 0.0004479
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.*22T>A		splice_region_variant	Exon 5 of 5	ENST00000343139.11	NP_002113.2
HLA-DQA1	NM_002122.5	c.*22T>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5	c.613+700T>A		intron_variant	Intron 3 of 3		XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.*22T>A		splice_region_variant	Exon 5 of 5	6	NM_002122.5	ENSP00000339398.5
HLA-DQA1	ENST00000343139.11	c.*22T>A		3_prime_UTR_variant	Exon 5 of 5	6	NM_002122.5	ENSP00000339398.5

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 409896 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 222972

African (AFR) AF: 0.00 AC: 0 AN: 12752

American (AMR) AF: 0.00 AC: 0 AN: 19016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12822

East Asian (EAS) AF: 0.00 AC: 0 AN: 23196

South Asian (SAS) AF: 0.00 AC: 0 AN: 51058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2630

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 240266

Other (OTH) AF: 0.00 AC: 0 AN: 22296

GnomAD4 genome Cov.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.57
PhyloP100		-0.78

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00045
dbscSNV1_RF	Benign	0.020
SpliceAI score (max)		0.040		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: rs9272863; hg19: chr6-32610730;