NM_001300790.2:c.758-112T>G

Variant names:

• chr6-32757416-A-C
• rs2301271
• NM_001300790.2:c.758-112T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001300790.2(HLA-DQB2):​c.758-112T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 795,194 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000067 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: HLA-DQB2 NM_001300790.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 66 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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.758-112T>G		intron	N/A	NP_001287719.1	Q5SR05
	HLA-DQB2	NM_001198858.2		c.647-112T>G		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.758-112T>G		intron	N/A	ENSP00000396330.2	Q5SR05
	HLA-DQB2	ENST00000435145.6	TSL:6	c.758-112T>G		intron	N/A	ENSP00000410512.2	A2ADX3
	HLA-DQB2	ENST00000870921.1		c.757+357T>G		intron	N/A	ENSP00000540980.1

Frequencies

GnomAD3 genomes AF: 0.00000672 AC: 1 AN: 148848 Hom.: 0 Cov.: 31

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: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000155 AC: 1 AN: 646346 Hom.: 0 AF XY: 0.00000294 AC XY: 1 AN XY: 340374

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16634

American (AMR) AF: 0.00 AC: 0 AN: 30584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18256

East Asian (EAS) AF: 0.00 AC: 0 AN: 32096

South Asian (SAS) AF: 0.00 AC: 0 AN: 57192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4054

European-Non Finnish (NFE) AF: 0.00000242 AC: 1 AN: 412528

Other (OTH) AF: 0.00 AC: 0 AN: 33044

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000672 AC: 1 AN: 148848 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 1 AN XY: 72724

African (AFR) AF: 0.00 AC: 0 AN: 40190

American (AMR) AF: 0.00 AC: 0 AN: 14900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3414

East Asian (EAS) AF: 0.00 AC: 0 AN: 5098

South Asian (SAS) AF: 0.00 AC: 0 AN: 4614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 66936

Other (OTH) AF: 0.00 AC: 0 AN: 2030

Alfa AF: 0.00 Hom.: 107141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.0
DANN	Benign	0.54
PhyloP100		0.29

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: rs2301271; hg19: chr6-32725193;