6-32638107-C-T

Variant names:

• chr6-32638107-C-T
• rs2187668
• NM_002122.5:c.82+567C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002122.5(HLA-DQA1):​c.82+567C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.0033 (8 hom., cov: 20)
• Consequence: HLA-DQA1 NM_002122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 282 publications found

Genes affected

HLA-DQA1 (HGNC:4942): (major histocompatibility complex, class II, DQ alpha 1) HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), 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. It is encoded by 5 exons; exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. [provided by RefSeq, Jul 2008]

HLA-DQA1-AS1 (HGNC:56667): (HLA-DQA1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002122.5. 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-DQA1	NM_002122.5	MANE Select	c.82+567C>T		intron	N/A	NP_002113.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA1	ENST00000343139.11	TSL:6 MANE Select	c.82+567C>T		intron	N/A	ENSP00000339398.5	P01909
	HLA-DQA1	ENST00000374949.2	TSL:6	c.82+567C>T		intron	N/A	ENSP00000364087.2	P01909
	HLA-DQA1	ENST00000395363.5	TSL:6	c.82+567C>T		intron	N/A	ENSP00000378767.1	P01909

Frequencies

GnomAD3 genomes AF: 0.00335 AC: 427 AN: 127434 Hom.: 9 Cov.: 20

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00247

Gnomad ASJ AF: 0.00256

Gnomad EAS AF: 0.00459

Gnomad SAS AF: 0.00474

Gnomad FIN AF: 0.00135

Gnomad MID AF: 0.0165

Gnomad NFE AF: 0.00492

Gnomad OTH AF: 0.00646

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00335 AC: 427 AN: 127560 Hom.: 8 Cov.: 20 AF XY: 0.00357 AC XY: 222 AN XY: 62154

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

African (AFR) AF: 0.00119 AC: 41 AN: 34554

American (AMR) AF: 0.00239 AC: 29 AN: 12148

Ashkenazi Jewish (ASJ) AF: 0.00256 AC: 8 AN: 3122

East Asian (EAS) AF: 0.00481 AC: 22 AN: 4572

South Asian (SAS) AF: 0.00422 AC: 16 AN: 3790

European-Finnish (FIN) AF: 0.00135 AC: 12 AN: 8920

Middle Eastern (MID) AF: 0.0179 AC: 4 AN: 224

European-Non Finnish (NFE) AF: 0.00492 AC: 284 AN: 57688

Other (OTH) AF: 0.00639 AC: 11 AN: 1722

⚠️ 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: 0.121 Hom.: 5515

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.33
PhyloP100		0.098
Mutation Taster		=100/0	polymorphism (auto)

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

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

Other links and lift over

dbSNP: rs2187668;

hg19: chr6-32605884;