Genetic Variant HLA-DOA:c.82+473C>G (chr6-33008982-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is The variant received 1 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Supporting

The NM_002119.4(HLA-DOA):c.82+473C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0000263 (AC=4) in the gnomAD database across 151,880 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.0000326. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Consequence

HLA-DOA
NM_002119.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.194

Publications

36 publications found

Variant links:

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]

HLA-DOA links:

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new If you want to explore the variant's impact on the transcript NM_002119.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 1 points.

Show applied only (1)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Very rare in gnomAD (popmax AF <0.01%) — O3 supporting; GnomAD effective popmax AF = 0.000033 — very rare (O3 supporting [+1])

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	HLA-DOA NM_002119.4	MANE Select	c.82+473C>G	intron	Intron 1 of 4	Prot: NP_002110.1 UniProt: P06340

HLA-DOA NM_002119.4

MANE Select

HGVSc / HGVSpc.82+473C>G

Exon rankIntron 1 of 4

intron

Prot: NP_002110.1UniProt: P06340

Ensembl Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
HLA-DOA ENST00000229829.7	TSL:6MANE Select	c.82+473C>G	intron	Intron 1 of 4	Prot: ENSP00000229829.3 UniProt: P06340
HLA-DOA ENST00000892664.1		c.82+473C>G	intron	Intron 1 of 3	Prot: ENSP00000562723.1 UniProt: A0ACI8QSL6
HLA-DOA ENST00000374813.1	TSL:6	c.82+473C>G	intron	Intron 1 of 2	Prot: ENSP00000363946.1 UniProt: F6WU08

HLA-DOA ENST00000229829.7

TSL:6MANE Select

HGVSc / HGVSpc.82+473C>G

Exon rankIntron 1 of 4

intron

Prot: ENSP00000229829.3UniProt: P06340

HLA-DOA ENST00000892664.1

HGVSc / HGVSpc.82+473C>G

Exon rankIntron 1 of 3

intron

Prot: ENSP00000562723.1UniProt: A0ACI8QSL6

HLA-DOA ENST00000374813.1

TSL:6

HGVSc / HGVSpc.82+473C>G

Exon rankIntron 1 of 2

intron

Prot: ENSP00000363946.1UniProt: F6WU08

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.0000263	AC:4	Hom:0	AN:151880	Cov:31
GnomAD4 genome	AF: 0.0000263	AC:4	Hom:0	AN:151880	Cov:31
TOPMed (Bravo)	AF: 0.0000491	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:110741	AN:631630	Cov:

Showing 4 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score
AlphaGenome AVI	Benign	3.3
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.22
GPN-Star LLR	N/A	3.2
GPN-Star score	N/A	-0.63
PhyloP100	Benign	-0.19

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence