ENST00000425797.2:n.1143G>A

Variant names:

• chr7-77000309-G-A
• rs1638152
• ENST00000425797.2:n.1143G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000425797.2(DTX2P1):​n.1143G>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 ENST00000425797.2 splice_region, non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 6 publications found

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]

ENSG00000299537 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000425797.2. 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
	DTX2P1-UPK3BP1-PMS2P11	NR_023383.1		n.541G>A		splice_region non_coding_transcript_exon	Exon 3 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTX2P1	ENST00000425797.2	TSL:6	n.1143G>A		splice_region non_coding_transcript_exon	Exon 5 of 8
	DTX2P1-UPK3BP1-PMS2P11	ENST00000579700.2	TSL:2	n.261G>A		splice_region non_coding_transcript_exon	Exon 3 of 11
	DTX2P1-UPK3BP1-PMS2P11	ENST00000584900.5	TSL:2	n.414G>A		splice_region non_coding_transcript_exon	Exon 3 of 11

Frequencies

GnomAD3 genomes AF: 0.363 AC: 44304 AN: 121904 Hom.: 5 Cov.: 32

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

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

African (AFR) AF: 0.315 AC: 6497 AN: 20600

American (AMR) AF: 0.380 AC: 13575 AN: 35760

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 7773 AN: 18984

East Asian (EAS) AF: 0.258 AC: 7189 AN: 27878

South Asian (SAS) AF: 0.411 AC: 28130 AN: 68502

European-Finnish (FIN) AF: 0.304 AC: 12823 AN: 42188

Middle Eastern (MID) AF: 0.418 AC: 1797 AN: 4296

European-Non Finnish (NFE) AF: 0.377 AC: 227207 AN: 603434

Other (OTH) AF: 0.365 AC: 13491 AN: 36996

⚠️ 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: InbreedingCoeff AF: 0.364 AC: 44357 AN: 122014 Hom.: 6 Cov.: 32 AF XY: 0.358 AC XY: 21425 AN XY: 59832

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

African (AFR) AF: 0.352 AC: 11216 AN: 31870

American (AMR) AF: 0.353 AC: 4334 AN: 12288

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1205 AN: 2872

East Asian (EAS) AF: 0.256 AC: 977 AN: 3816

South Asian (SAS) AF: 0.388 AC: 1474 AN: 3796

European-Finnish (FIN) AF: 0.284 AC: 2439 AN: 8602

Middle Eastern (MID) AF: 0.390 AC: 78 AN: 200

European-Non Finnish (NFE) AF: 0.387 AC: 21721 AN: 56154

Other (OTH) AF: 0.377 AC: 638 AN: 1694

⚠️ 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: 0.234 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.93
PhyloP100		1.7

Splicing

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

Other links and lift over

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