6-32761931-G-A

Variant names:

• chr6-32761931-G-A
• rs140805830
• NM_001300790.2:c.98-5C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300790.2. 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-DQB2	NM_001300790.2	MANE Select	c.98-5C>T		splice_region intron	N/A	NP_001287719.1	Q5SR05
	HLA-DQB2	NM_001198858.2		c.98-5C>T		splice_region intron	N/A	NP_001185787.1	P05538-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQB2	ENST00000437316.7	TSL:6 MANE Select	c.98-5C>T		splice_region intron	N/A	ENSP00000396330.2	Q5SR05
	HLA-DQB2	ENST00000435145.6	TSL:6	c.98-5C>T		splice_region intron	N/A	ENSP00000410512.2	A2ADX3
	HLA-DQB2	ENST00000870921.1		c.98-5C>T		splice_region intron	N/A	ENSP00000540980.1

Frequencies

GnomAD3 genomes AF: 0.00909 AC: 1384 AN: 152234 Hom.: 11 Cov.: 34

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

GnomAD2 exomes AF: 0.00506 AC: 1154 AN: 227988 AF XY: 0.00576

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 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.: 45 Cov.: 63 AF XY: 0.00295 AC XY: 2130 AN XY: 721942

African (AFR) AF: 0.0239 AC: 789 AN: 33030

American (AMR) AF: 0.00259 AC: 114 AN: 43964

Ashkenazi Jewish (ASJ) AF: 0.000653 AC: 17 AN: 26024

East Asian (EAS) AF: 0.000975 AC: 38 AN: 38988

South Asian (SAS) AF: 0.0174 AC: 1474 AN: 84584

European-Finnish (FIN) AF: 0.0000385 AC: 2 AN: 51918

Middle Eastern (MID) AF: 0.0160 AC: 91 AN: 5688

European-Non Finnish (NFE) AF: 0.000841 AC: 932 AN: 1108320

Other (OTH) AF: 0.00348 AC: 209 AN: 60068

GnomAD4 genome AF: 0.00916 AC: 1395 AN: 152352 Hom.: 11 Cov.: 34 AF XY: 0.00872 AC XY: 650 AN XY: 74508

African (AFR) AF: 0.0278 AC: 1156 AN: 41580

American (AMR) AF: 0.00372 AC: 57 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5186

South Asian (SAS) AF: 0.0143 AC: 69 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00119 AC: 81 AN: 68032

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00482 Hom.: 5

Bravo AF: 0.00969

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		0.40
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs140805830; hg19: chr6-32729708;