rs2251824

Variant names:

• chr6-31544080-G-A
• rs2251824
• ENST00000376185.5:n.184-1932C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000376185.5(ATP6V1G2-DDX39B):​n.184-1932C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,084 control chromosomes in the GnomAD database, including 1,752 homozygotes. 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 0.15 (1752 hom., cov: 32)
• Consequence: ATP6V1G2-DDX39B ENST00000376185.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717
• Publications: 30 publications found

Genes affected

ATP6V1G2-DDX39B (HGNC:41999): (ATP6V1G2-DDX39B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) and DDX39B (DEAD box polypeptide 39B) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript and is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6V1G2-DDX39B	NR_037853.1	n.473-1932C>T		intron_variant	Intron 2 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1G2-DDX39B	ENST00000376185.5	n.184-1932C>T		intron_variant	Intron 2 of 12	2		ENSP00000365356.1
ATP6V1G2-DDX39B	ENST00000475917.1	n.278+618C>T		intron_variant	Intron 3 of 3	4
ATP6V1G2-DDX39B	ENST00000480131.1	n.184-1932C>T		intron_variant	Intron 2 of 3	4		ENSP00000420191.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22539 AN: 151966 Hom.: 1754 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.148 AC: 22550 AN: 152084 Hom.: 1752 Cov.: 32 AF XY: 0.150 AC XY: 11148 AN XY: 74328

African (AFR) AF: 0.119 AC: 4921 AN: 41498

American (AMR) AF: 0.135 AC: 2061 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 515 AN: 3470

East Asian (EAS) AF: 0.161 AC: 837 AN: 5184

South Asian (SAS) AF: 0.249 AC: 1199 AN: 4820

European-Finnish (FIN) AF: 0.179 AC: 1892 AN: 10560

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10714 AN: 67946

Other (OTH) AF: 0.162 AC: 342 AN: 2112

Alfa AF: 0.158 Hom.: 7627

Bravo AF: 0.144

Asia WGS AF: 0.224 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.34
DANN	Benign	0.78
PhyloP100		-0.72

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: rs2251824; hg19: chr6-31511857;