chr6-32744005-A-G

Variant names:

• chr6-32744005-A-G
• rs2227127
• NM_020056.5:c.83-1154A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020056.5(HLA-DQA2):​c.83-1154A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,006 control chromosomes in the GnomAD database, including 11,947 homozygotes. 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 0.38 (11947 hom., cov: 32)
• Consequence: HLA-DQA2 NM_020056.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 22 publications found

Genes affected

HLA-DQA2 (HGNC:4943): (major histocompatibility complex, class II, DQ alpha 2) This gene belongs to the HLA class II alpha chain family. The encoded protein forms a heterodimer with a class II beta chain. It is located in intracellular vesicles and plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (B lymphocytes, dendritic cells, macrophages) and are used to present antigenic peptides on the cell surface to be recognized by CD4 T-cells. [provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020056.5. 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-DQA2	NM_020056.5	MANE Select	c.83-1154A>G		intron	N/A	NP_064440.1	P01906

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA2	ENST00000374940.4	TSL:6 MANE Select	c.83-1154A>G		intron	N/A	ENSP00000364076.3	P01906

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57062 AN: 151888 Hom.: 11938 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.367

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.376 AC: 57104 AN: 152006 Hom.: 11947 Cov.: 32 AF XY: 0.384 AC XY: 28547 AN XY: 74274

African (AFR) AF: 0.205 AC: 8504 AN: 41460

American (AMR) AF: 0.435 AC: 6659 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1348 AN: 3460

East Asian (EAS) AF: 0.611 AC: 3161 AN: 5174

South Asian (SAS) AF: 0.489 AC: 2349 AN: 4802

European-Finnish (FIN) AF: 0.538 AC: 5668 AN: 10536

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.410 AC: 27875 AN: 67966

Other (OTH) AF: 0.376 AC: 793 AN: 2110

Alfa AF: 0.313 Hom.: 3243

Bravo AF: 0.362

Asia WGS AF: 0.547 AC: 1898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.46
PhyloP100		0.16
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

Other links and lift over

dbSNP: rs2227127; hg19: chr6-32711782;