Genetic Variant HLA-DMA:c.374-314C>A (chr6-32950203-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006120.4(HLA-DMA):c.374-314C>A 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: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HLA-DMA
NM_006120.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Publications

0 publications found

Variant links:

Genes affected

HLA-DMA (HGNC:4934): (major histocompatibility complex, class II, DM alpha) HLA-DMA belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta chain (DMB), 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 molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and the cytoplasmic tail. [provided by RefSeq, Jul 2008]

HLA-DMA links:

ENSG00000248993 (HGNC:):

ENSG00000248993 links:

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ACMG classification

Classification was made for transcript

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DMA	NM_006120.4 link	c.374-314C>A		intron_variant	Intron 2 of 4	ENST00000374843.9	NP_006111.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DMA	ENST00000374843.9 link	c.374-314C>A		intron_variant	Intron 2 of 4	6	NM_006120.4	ENSP00000363976.4
ENSG00000248993	ENST00000429234.1 link	c.88+2746C>A		intron_variant	Intron 1 of 3	2		ENSP00000412457.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

438010

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

229912

African (AFR)

AF:

0.00

AC:

AN:

12300

American (AMR)

AF:

0.00

AC:

AN:

17856

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13612

East Asian (EAS)

AF:

0.00

AC:

AN:

30578

South Asian (SAS)

AF:

0.00

AC:

AN:

42288

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28876

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1950

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

264908

Other (OTH)

AF:

0.00

AC:

AN:

25642

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0040

(source)

DANN

Benign

0.39

PhyloP100

-1.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over