Variant chr6-32761931-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001300790.2(HLA-DQB2):c.98-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,604,936 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0092 ( 11 hom., cov: 34)

Exomes 𝑓: 0.0025 ( 45 hom. )

Consequence

HLA-DQB2
NM_001300790.2 splice_region, intron

Scores

Splicing: ADA: 0.0001847

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.399

Variant links:

Genes affected

HLA-DQB2 (HGNC:4945): (major histocompatibility complex, class II, DQ beta 2) HLA-DQB2 belongs to the family of HLA class II beta chain paralogs. Class II molecules are heterodimers consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. They play 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). Polymorphisms in the alpha and beta chains specify the peptide binding specificity, and typing for these polymorphisms is routinely done for bone marrow transplantation. However this gene, HLA-DQB2, is not routinely typed, as it is not thought to have an effect on transplantation. There is conflicting evidence in the literature and public sequence databases for the protein-coding capacity of HLA-DQB2. Because there is evidence of transcription and an intact ORF, HLA-DQB2 is represented in Entrez Gene and in RefSeq as a protein-coding locus. [provided by RefSeq, Oct 2010]

HLA-DQB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 6-32761931-G-A is Benign according to our data. Variant chr6-32761931-G-A is described in ClinVar as [Benign]. Clinvar id is 785166.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00916 (1395/152352) while in subpopulation AFR AF= 0.0278 (1156/41580). AF 95% confidence interval is 0.0265. There are 11 homozygotes in gnomad4. There are 650 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQB2	NM_001300790.2 link	c.98-5C>T		splice_region_variant, intron_variant		ENST00000437316.7	NP_001287719.1	Q5SR05

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
HLA-DQB2	ENST00000437316.7 link	c.98-5C>T	splice_region_variant, intron_variant	6	NM_001300790.2	ENSP00000396330.2	Q5SR05
HLA-DQB2	ENST00000435145.6 link	c.98-5C>T	splice_region_variant, intron_variant	6		ENSP00000410512.2	A2ADX3
HLA-DQB2	ENST00000411527.5 link	c.98-5C>T	splice_region_variant, intron_variant	6		ENSP00000390431.1	P05538-2
HLA-DQB2	ENST00000427449.1 link	c.92-5C>T	splice_region_variant, intron_variant	6		ENSP00000415997.1	H0Y7Y7

Frequencies

GnomAD3 genomes

AF:

0.00909

AC:

1384

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0276

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.00506

AC:

1154

AN:

227988

Hom.:

AF XY:

0.00576

AC XY:

718

AN XY:

124746

show subpopulations

Gnomad AFR exome

AF:

0.0270

Gnomad AMR exome

AF:

0.00241

Gnomad ASJ exome

AF:

0.00103

Gnomad EAS exome

AF:

0.00187

Gnomad SAS exome

AF:

0.0196

Gnomad FIN exome

AF:

0.000193

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.00367

GnomAD4 exome

AF:

0.00252

AC:

3666

AN:

1452584

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

2130

AN XY:

721942

show subpopulations

Gnomad4 AFR exome

AF:

0.0239

Gnomad4 AMR exome

AF:

0.00259

Gnomad4 ASJ exome

AF:

0.000653

Gnomad4 EAS exome

AF:

0.000975

Gnomad4 SAS exome

AF:

0.0174

Gnomad4 FIN exome

AF:

0.0000385

Gnomad4 NFE exome

AF:

0.000841

Gnomad4 OTH exome

AF:

0.00348

GnomAD4 genome

AF:

0.00916

AC:

1395

AN:

152352

Hom.:

Cov.:

AF XY:

0.00872

AC XY:

650

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0278

Gnomad4 AMR

AF:

0.00372

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0143

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00119

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.00482

Hom.:

Bravo

AF:

0.00969

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00018

dbscSNV1_RF

Benign

0.038

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over