Variant 6-32664795-CACCTCTCCTCTG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP5_ModerateBS2

The NM_002123.5(HLA-DQB1):c.370_379+2delCAGAGGAGAGGT(p.Gln124fs) variant causes a frameshift, splice donor, splice region, intron change. The variant allele was found at a frequency of 0.0000563 in 922,916 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 13)

Exomes 𝑓: 0.000056 ( 5 hom. )

Failed GnomAD Quality Control

Consequence

HLA-DQB1
NM_002123.5 frameshift, splice_donor, splice_region, intron

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 5.84

Variant links:

Genes affected

HLA-DQB1 (HGNC:4944): (major histocompatibility complex, class II, DQ beta 1) HLA-DQB1 belongs to the HLA class II beta chain paralogs. This 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 beta chain is approximately 26-28 kDa and it contains six exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

HLA-DQB1 links:

HLA-DQB1 (HGNC:):

HLA-DQB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP5

Variant 6-32664795-CACCTCTCCTCTG-C is Pathogenic according to our data. Variant chr6-32664795-CACCTCTCCTCTG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3256932.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQB1	NM_002123.5 linkuse as main transcript	c.370_379+2delCAGAGGAGAGGT	p.Gln124fs	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	2/5	ENST00000434651.7	NP_002114.3	P01920Q5Y7D6Q5Y7A9
HLA-DQB1	NM_001243961.2 linkuse as main transcript	c.370_379+2delCAGAGGAGAGGT	p.Gln124fs	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	2/6		NP_001230890.1	Q5SU54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQB1	ENST00000434651.7 linkuse as main transcript	c.370_379+2delCAGAGGAGAGGT	p.Gln124fs	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	2/5	6	NM_002123.5	ENSP00000407332.2		Q5Y7D6
HLA-DQB1	ENST00000374943.8 linkuse as main transcript	c.370_379+2delCAGAGGAGAGGT	p.Gln124fs	frameshift_variant, splice_donor_variant, splice_region_variant, intron_variant	2/6	6		ENSP00000364080.4		Q5SU54

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

111744

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000563

AC:

AN:

922916

Hom.:

AF XY:

0.0000855

AC XY:

AN XY:

468066

show subpopulations

Gnomad4 AFR exome

AF:

0.0000861

Gnomad4 AMR exome

AF:

0.0000880

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000153

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000659

Gnomad4 OTH exome

AF:

0.0000494

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

111834

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

54410

Gnomad4 AFR

AF:

0.00

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Susceptibility to severe COVID-19

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Molecular Medicine Center, Medical University of Sofia

Jul 22, 2024

Novel (unreported in gnomAD or dbSNP until April 2024) variant found in severely infected COVID-19 Bulgarian patients in a research study. Variant is classified as likely pathogenic according to the ACMG criteria: PM2,PVS1. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over