rs2239527

Variant names:

• chr6-31542002-C-G
• rs2239527
• ENST00000376185.5:n.*30G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-31542002-C-G
• chr6-31542002-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The ENST00000376185.5(ATP6V1G2-DDX39B):​n.*30G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 679,910 control chromosomes in the GnomAD database, including 40,492 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 0.37 (11097 hom., cov: 33)
  • Exomes 𝑓: 0.32 (29395 hom.)
• Consequence: ATP6V1G2-DDX39B ENST00000376185.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35
• 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]

DDX39B (HGNC:13917): (DExD-box helicase 39B) This gene encodes a member of the DEAD box family of RNA-dependent ATPases that mediate ATP hydrolysis during pre-mRNA splicing. The encoded protein is an essential splicing factor required for association of U2 small nuclear ribonucleoprotein with pre-mRNA, and it also plays an important role in mRNA export from the nucleus to the cytoplasm. This gene belongs to a cluster of genes localized in the vicinity of the genes encoding tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. Mutations in this gene may be associated with rheumatoid arthritis. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on both chromosomes 6 and 11. Read-through transcription also occurs between this gene and the upstream ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) gene. [provided by RefSeq, Feb 2011]

DDX39B Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000299760 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX39B	NM_004640.7	c.-185G>C		5_prime_UTR_variant	Exon 1 of 11	ENST00000396172.6	NP_004631.1
DDX39B	NR_037852.2	n.2G>C		non_coding_transcript_exon_variant	Exon 1 of 9
ATP6V1G2-DDX39B	NR_037853.1	n.619G>C		non_coding_transcript_exon_variant	Exon 3 of 13
DDX39B	NM_080598.6	c.-55G>C		5_prime_UTR_variant	Exon 1 of 11		NP_542165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1G2-DDX39B	ENST00000376185.5	n.*30G>C		non_coding_transcript_exon_variant	Exon 3 of 13	2		ENSP00000365356.1
DDX39B	ENST00000396172.6	c.-185G>C		5_prime_UTR_variant	Exon 1 of 11	1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*30G>C		3_prime_UTR_variant	Exon 3 of 13	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56889 AN: 152014 Hom.: 11087 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.341

GnomAD2 exomes AF: 0.328 AC: 43943 AN: 133932 AF XY: 0.318

Gnomad AFR exome AF: 0.490

Gnomad AMR exome AF: 0.336

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.503

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.336

Gnomad OTH exome AF: 0.333

GnomAD4 exome AF: 0.324 AC: 171224 AN: 527778 Hom.: 29395 Cov.: 0 AF XY: 0.315 AC XY: 88690 AN XY: 281824

African (AFR) AF: 0.488 AC: 7459 AN: 15270

American (AMR) AF: 0.331 AC: 11100 AN: 33554

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 5098 AN: 19706

East Asian (EAS) AF: 0.422 AC: 13264 AN: 31402

South Asian (SAS) AF: 0.201 AC: 12452 AN: 62064

European-Finnish (FIN) AF: 0.318 AC: 10637 AN: 33448

Middle Eastern (MID) AF: 0.325 AC: 1094 AN: 3370

European-Non Finnish (NFE) AF: 0.334 AC: 100136 AN: 299576

Other (OTH) AF: 0.340 AC: 9984 AN: 29388

GnomAD4 genome AF: 0.374 AC: 56931 AN: 152132 Hom.: 11097 Cov.: 33 AF XY: 0.369 AC XY: 27471 AN XY: 74390

African (AFR) AF: 0.487 AC: 20189 AN: 41486

American (AMR) AF: 0.340 AC: 5205 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 870 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2424 AN: 5166

South Asian (SAS) AF: 0.214 AC: 1035 AN: 4830

European-Finnish (FIN) AF: 0.302 AC: 3201 AN: 10592

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22863 AN: 67986

Other (OTH) AF: 0.339 AC: 713 AN: 2104

Alfa AF: 0.267 Hom.: 1051

Bravo AF: 0.383

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	20
DANN	Benign	0.94
PhyloP100		3.3
PromoterAI		-0.043	Neutral
Mutation Taster		=299/1	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

Other links and lift over

dbSNP: rs2239527; hg19: chr6-31509779; COSMIC: COSV58214051; COSMIC: COSV58214051;