Variant rs2308911 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001242525.2(HLA-DPA1):c.184A>C(p.Met62Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,579,094 control chromosomes in the GnomAD database, including 45,154 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M62K) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.28 ( 8068 hom., cov: 32)

Exomes 𝑓: 0.20 ( 37086 hom. )

Consequence

HLA-DPA1
NM_001242525.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.58

Variant links:

Genes affected

HLA-DPA1 (HGNC:4938): (major histocompatibility complex, class II, DP alpha 1) HLA-DPA1 belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta (DPB) chain, both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. 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. Within the DP molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules. [provided by RefSeq, Jul 2008]

HLA-DPA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.9242078E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HLA-DPA1	NM_033554.4 linkuse as main transcript	c.184A>C	p.Met62Leu	missense_variant	2/5	ENST00000692443.1
HLA-DPA1	NM_001242525.2 linkuse as main transcript	c.184A>C	p.Met62Leu	missense_variant	3/6
HLA-DPA1	NM_001242524.2 linkuse as main transcript	c.184A>C	p.Met62Leu	missense_variant	3/6
HLA-DPA1	NM_001405020.1 linkuse as main transcript	c.184A>C	p.Met62Leu	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DPA1	ENST00000692443.1 linkuse as main transcript	c.184A>C	p.Met62Leu	missense_variant	2/5		NM_033554.4	P1

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43197

AN:

151830

Hom.:

8052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.486

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.661

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.175

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.299

GnomAD3 exomes

AF:

0.232

AC:

55816

AN:

240502

Hom.:

9863

AF XY:

0.230

AC XY:

30143

AN XY:

130920

show subpopulations

Gnomad AFR exome

AF:

0.498

Gnomad AMR exome

AF:

0.163

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.655

Gnomad SAS exome

AF:

0.303

Gnomad FIN exome

AF:

0.0982

Gnomad NFE exome

AF:

0.162

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.196

AC:

279366

AN:

1427146

Hom.:

37086

Cov.:

AF XY:

0.199

AC XY:

141150

AN XY:

711022

show subpopulations

Gnomad4 AFR exome

AF:

0.507

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.172

Gnomad4 EAS exome

AF:

0.622

Gnomad4 SAS exome

AF:

0.307

Gnomad4 FIN exome

AF:

0.102

Gnomad4 NFE exome

AF:

0.166

Gnomad4 OTH exome

AF:

0.224

GnomAD4 genome

AF:

0.285

AC:

43242

AN:

151948

Hom.:

8068

Cov.:

AF XY:

0.282

AC XY:

20953

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.486

Gnomad4 AMR

AF:

0.243

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.662

Gnomad4 SAS

AF:

0.335

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.175

Gnomad4 OTH

AF:

0.305

Alfa

AF:

0.182

Hom.:

1741

Bravo

AF:

0.303

ESP6500AA

AF:

0.0149

AC:

ESP6500EA

AF:

0.00129

AC:

ExAC

AF:

0.239

AC:

28100

Asia WGS

AF:

0.432

AC:

1503

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.0010

DANN

Benign

0.24

DEOGEN2

Benign

0.00051

T;.

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0089

MetaRNN

Benign

0.0000029

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.015

N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.13

N;N

REVEL

Benign

0.063

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;.

Polyphen

0.0

B;.

Vest4

0.075

MutPred

0.066

Gain of phosphorylation at Y64 (P = 0.0928);Gain of phosphorylation at Y64 (P = 0.0928);

MPC

0.44

ClinPred

0.0000096

GERP RS

-6.0

Varity_R

0.24

gMVP

0.31

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over