6-33006774-G-T

Variant names:

• chr6-33006774-G-T
• rs2582
• NM_002119.4:c.*64C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002119.4(HLA-DOA):​c.*64C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,611,676 control chromosomes in the GnomAD database, including 15,983 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 0.11 (1166 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14817 hom.)
• Consequence: HLA-DOA NM_002119.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 35 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.033).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002119.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DOA	NM_002119.4	MANE Select	c.*64C>A		3_prime_UTR	Exon 5 of 5	NP_002110.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DOA	ENST00000229829.7	TSL:6 MANE Select	c.*64C>A		3_prime_UTR	Exon 5 of 5	ENSP00000229829.3
	HLA-DOA	ENST00000490305.5	TSL:6	n.235C>A		non_coding_transcript_exon	Exon 3 of 3
	HLA-DOA	ENST00000485901.1	TSL:6	n.*27C>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16226 AN: 152106 Hom.: 1164 Cov.: 32

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.129

GnomAD2 exomes AF: 0.144 AC: 35485 AN: 246622 AF XY: 0.152

Gnomad AFR exome AF: 0.0227

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.196

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.165

GnomAD4 exome AF: 0.130 AC: 189993 AN: 1459452 Hom.: 14817 Cov.: 31 AF XY: 0.135 AC XY: 98135 AN XY: 726154

African (AFR) AF: 0.0230 AC: 771 AN: 33468

American (AMR) AF: 0.107 AC: 4764 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 7090 AN: 26114

East Asian (EAS) AF: 0.277 AC: 10997 AN: 39690

South Asian (SAS) AF: 0.245 AC: 21143 AN: 86210

European-Finnish (FIN) AF: 0.109 AC: 5707 AN: 52270

Middle Eastern (MID) AF: 0.199 AC: 1148 AN: 5762

European-Non Finnish (NFE) AF: 0.117 AC: 129947 AN: 1110872

Other (OTH) AF: 0.140 AC: 8426 AN: 60350

GnomAD4 genome AF: 0.107 AC: 16226 AN: 152224 Hom.: 1166 Cov.: 32 AF XY: 0.111 AC XY: 8226 AN XY: 74408

African (AFR) AF: 0.0241 AC: 1001 AN: 41544

American (AMR) AF: 0.114 AC: 1749 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3468

East Asian (EAS) AF: 0.209 AC: 1080 AN: 5176

South Asian (SAS) AF: 0.231 AC: 1115 AN: 4828

European-Finnish (FIN) AF: 0.114 AC: 1204 AN: 10594

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8709 AN: 68008

Other (OTH) AF: 0.132 AC: 278 AN: 2110

Alfa AF: 0.129 Hom.: 3707

Bravo AF: 0.101

Asia WGS AF: 0.246 AC: 855 AN: 3478

EpiCase AF: 0.145

EpiControl AF: 0.145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.57
PhyloP100		1.6
Mutation Taster		=97/3	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: rs2582; hg19: chr6-32974551; COSMIC: COSV57713597; COSMIC: COSV57713597;