rs200936222

Variant names:

• chr6-32745293-A-C
• rs200936222
• NM_020056.5:c.217A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-32745293-A-C
• chr6-32745293-A-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_020056.5(HLA-DQA2):​c.217A>C​(p.Met73Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.014 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00013 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA2 NM_020056.5 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.52
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040393054).
• BP6: Variant 6-32745293-A-C is Benign according to our data. Variant chr6-32745293-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2681313.Status of the report is no_assertion_criteria_provided, 0 stars.

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>C	p.Met73Leu	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>C	p.Met73Leu	missense	Exon 2 of 5	ENSP00000364076.3	P01906

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 1751 AN: 123438 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00885

Gnomad AMI AF: 0.0279

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.0188

Gnomad EAS AF: 0.0251

Gnomad SAS AF: 0.0158

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0144

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 250438 AF XY: 0.0000221

Gnomad AFR exome AF: 0.0000624

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000134 AC: 190 AN: 1422528 Hom.: 1 Cov.: 41 AF XY: 0.000132 AC XY: 93 AN XY: 706240

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32658

American (AMR) AF: 0.0000240 AC: 1 AN: 41622

Ashkenazi Jewish (ASJ) AF: 0.000160 AC: 4 AN: 24940

East Asian (EAS) AF: 0.000131 AC: 5 AN: 38256

South Asian (SAS) AF: 0.000260 AC: 21 AN: 80896

European-Finnish (FIN) AF: 0.00192 AC: 97 AN: 50498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5504

European-Non Finnish (NFE) AF: 0.0000514 AC: 56 AN: 1089662

Other (OTH) AF: 0.000103 AC: 6 AN: 58492

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0142 AC: 1754 AN: 123530 Hom.: 0 Cov.: 30 AF XY: 0.0138 AC XY: 839 AN XY: 60596

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00888 AC: 312 AN: 35138

American (AMR) AF: 0.0150 AC: 185 AN: 12342

Ashkenazi Jewish (ASJ) AF: 0.0188 AC: 52 AN: 2764

East Asian (EAS) AF: 0.0252 AC: 102 AN: 4048

South Asian (SAS) AF: 0.0158 AC: 62 AN: 3930

European-Finnish (FIN) AF: 0.0137 AC: 121 AN: 8818

Middle Eastern (MID) AF: 0.00917 AC: 2 AN: 218

European-Non Finnish (NFE) AF: 0.0162 AC: 874 AN: 53834

Other (OTH) AF: 0.0142 AC: 25 AN: 1758

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0200 Hom.: 0

ExAC AF: 0.000437 AC: 53

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	EBV-positive nodal T- and NK-cell lymphoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.048
DANN	Benign	0.34
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0035	N
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.18	N
PhyloP100		-2.5
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.023
Sift	Benign	1.0	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.48		Gain of catalytic residue at M73 (P = 0.0059)
MVP		0.099
MPC		0.38
ClinPred		0.032	T
GERP RS		-6.1
Varity_R		0.10
gMVP		0.22
Mutation Taster		=99/1	polymorphism

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: rs200936222; hg19: chr6-32713070; COSMIC: COSV66566480; COSMIC: COSV66566480;