rs2284191

Variant names:

• chr6-33008877-G-A
• rs2284191
• NM_002119.4:c.82+578C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002119.4(HLA-DOA):​c.82+578C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 152,144 control chromosomes in the GnomAD database, including 601 homozygotes. 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 0.076 (601 hom., cov: 32)
• Consequence: HLA-DOA NM_002119.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990
• Publications: 29 publications found

Genes affected

HLA-DOA (HGNC:4936): (major histocompatibility complex, class II, DO alpha) HLA-DOA belongs to the HLA class II alpha chain paralogues. HLA-DOA forms a heterodimer with HLA-DOB. The heterodimer, HLA-DO, is found in lysosomes in B cells and regulates HLA-DM-mediated peptide loading on MHC class II molecules. In comparison with classical HLA class II molecules, this gene exhibits very little sequence variation, especially at the protein level. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DOA	NM_002119.4	c.82+578C>T		intron_variant	Intron 1 of 4	ENST00000229829.7	NP_002110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DOA	ENST00000229829.7	c.82+578C>T		intron_variant	Intron 1 of 4	6	NM_002119.4	ENSP00000229829.3
HLA-DOA	ENST00000374813.1	c.82+578C>T		intron_variant	Intron 1 of 2	6		ENSP00000363946.1
HLA-DOA	ENST00000467465.1	n.129-473C>T		intron_variant	Intron 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.0765 AC: 11631 AN: 152026 Hom.: 600 Cov.: 32

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0890

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0873

Gnomad OTH AF: 0.0660

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0765 AC: 11633 AN: 152144 Hom.: 601 Cov.: 32 AF XY: 0.0811 AC XY: 6032 AN XY: 74358

African (AFR) AF: 0.0266 AC: 1104 AN: 41500

American (AMR) AF: 0.0635 AC: 972 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 327 AN: 3472

East Asian (EAS) AF: 0.111 AC: 575 AN: 5186

South Asian (SAS) AF: 0.0893 AC: 430 AN: 4816

European-Finnish (FIN) AF: 0.196 AC: 2069 AN: 10556

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0873 AC: 5937 AN: 67996

Other (OTH) AF: 0.0648 AC: 137 AN: 2114

Alfa AF: 0.0825 Hom.: 2423

Bravo AF: 0.0639

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.41
PhyloP100		0.099
Mutation Taster		=100/0	polymorphism (auto)

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: rs2284191; hg19: chr6-32976654;