rs1638152

Positions:

• chr7-77000309-G-A
• chr7-77000309-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000579700.1(DTX2P1-UPK3BP1-PMS2P11):​n.261G>A variant causes a splice region, non coding transcript exon 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 0.36 (6 hom., cov: 32)
  • Exomes 𝑓: 0.37 (53 hom.)
  • Failed GnomAD Quality Control
• Consequence: DTX2P1-UPK3BP1-PMS2P11 ENST00000579700.1 splice_region, non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

Genes affected

DTX2P1 (HGNC:42352): (DTX2 pseudogene 1)

DTX2P1-UPK3BP1-PMS2P11 (HGNC:42360): (DTX2P1-UPK3BP1-PMS2P11 readthrough, transcribed pseudogene) This locus represents naturally-occurring readthrough transcription spanning multiple pseudogenes: DTX2P1 (DTX2 pseudogene 1), UPK3BP1 (uroplakin 3B pseudogene 1), PMS2P11 (PMS1 homolog 2, mismatch repair system component pseudogene 11). Some transcripts may also extend to PMS2P9 (PMS1 homolog 2, mismatch repair system component pseudogene 9). The readthrough transcripts likely do not encode functional proteins. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTX2P1-UPK3BP1-PMS2P11	NR_023383.1	n.541G>A		splice_region_variant, non_coding_transcript_exon_variant	3/11
DTX2P1		n.77000309G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTX2P1	ENST00000425797.2	n.1143G>A		splice_region_variant, non_coding_transcript_exon_variant	5/8	6
DTX2P1-UPK3BP1-PMS2P11	ENST00000579700.1	n.261G>A		splice_region_variant, non_coding_transcript_exon_variant	3/9	2
DTX2P1-UPK3BP1-PMS2P11	ENST00000584900.5	n.414G>A		splice_region_variant, non_coding_transcript_exon_variant	3/11	2
DTX2P1-UPK3BP1-PMS2P11	ENST00000636308.1	n.1371G>A		splice_region_variant, non_coding_transcript_exon_variant	6/15	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 44304 AN: 121904 Hom.: 5 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.388

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.375

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.371 AC: 318482 AN: 858638 Hom.: 53 Cov.: 15 AF XY: 0.374 AC XY: 166391 AN XY: 444616

Gnomad4 AFR exome AF: 0.315

Gnomad4 AMR exome AF: 0.380

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.411

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.377

Gnomad4 OTH exome AF: 0.365

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.364 AC: 44357 AN: 122014 Hom.: 6 Cov.: 32 AF XY: 0.358 AC XY: 21425 AN XY: 59832

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.377

Alfa AF: 0.234 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.93

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1638152; hg19: chr7-76629626; COSMIC: COSV50830724;