Genetic Variant NM_020056.5:c.217A>G (chr6-32745293-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020056.5(HLA-DQA2):c.217A>G(p.Met73Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,443,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M73L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

HLA-DQA2
NM_020056.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.52

Publications

9 publications found

Variant links:

Genes affected

HLA-DQA2 (HGNC:4943): (major histocompatibility complex, class II, DQ alpha 2) This gene belongs to the HLA class II alpha chain family. The encoded protein forms a heterodimer with a class II beta chain. It is located in intracellular vesicles and 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 (B lymphocytes, dendritic cells, macrophages) and are used to present antigenic peptides on the cell surface to be recognized by CD4 T-cells. [provided by RefSeq, Jun 2010]

HLA-DQA2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07064676).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020056.5. 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-DQA2	NM_020056.5	MANE Select	c.217A>G	p.Met73Val	missense	Exon 2 of 5	NP_064440.1	P01906

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA2	ENST00000374940.4	TSL:6 MANE Select	c.217A>G	p.Met73Val	missense	Exon 2 of 5	ENSP00000364076.3	P01906

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1443590

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717800

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33064

American (AMR)

AF:

0.00

AC:

AN:

43140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25564

East Asian (EAS)

AF:

0.00

AC:

AN:

39014

South Asian (SAS)

AF:

0.00

AC:

AN:

84224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.00000272

AC:

AN:

1101348

Other (OTH)

AF:

0.00

AC:

AN:

59418

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.022

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.00082

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.00066

M_CAP

Benign

0.0027

MetaRNN

Benign

0.071

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.29

PhyloP100

-2.5

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.22

REVEL

Benign

0.0060

Sift

Benign

0.62

Sift4G

Benign

0.14

Polyphen

0.0

Vest4

0.074

MutPred

0.43

Gain of relative solvent accessibility (P = 0.09)

MVP

0.12

MPC

0.41

ClinPred

0.16

GERP RS

-6.1

Varity_R

0.065

gMVP

0.25

Mutation Taster

=99/1

polymorphism

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over