rs2071556

Variant names:

• chr6-32936824-G-A
• rs2071556
• NM_002118.5:c.622+348C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32936824-G-A
• chr6-32936824-G-C
• chr6-32936824-G-T

Variant summary

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

The NM_002118.5(HLA-DMB):​c.622+348C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DMB NM_002118.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 34 publications found

Genes affected

HLA-DMB (HGNC:4935): (major histocompatibility complex, class II, DM beta) HLA-DMB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta (DMB) chain, both anchored in the membrane. It is located in intracellular vesicles. DM plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP (class II-associated invariant chain peptide) molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one 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. [provided by RefSeq, Jul 2008]

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=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002118.5. 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-DMB	NM_002118.5	MANE Select	c.622+348C>T		intron	N/A	NP_002109.2	P28068

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DMB	ENST00000418107.3	TSL:6 MANE Select	c.622+348C>T		intron	N/A	ENSP00000398890.2	P28068
	HLA-DMB	ENST00000863465.1		c.622+348C>T		intron	N/A	ENSP00000533524.1
	HLA-DMB	ENST00000863464.1		c.481+489C>T		intron	N/A	ENSP00000533523.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 62072 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 31290

African (AFR) AF: 0.00 AC: 0 AN: 2370

American (AMR) AF: 0.00 AC: 0 AN: 1742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2718

East Asian (EAS) AF: 0.00 AC: 0 AN: 5478

South Asian (SAS) AF: 0.00 AC: 0 AN: 690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 352

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 40762

Other (OTH) AF: 0.00 AC: 0 AN: 4420

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 109688

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.93
PhyloP100		0.043

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: rs2071556; hg19: chr6-32904601;