rs606231226

Variant names:

• chr7-154305155-C-T
• rs606231226
• ENST00000462622.5:n.46C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The ENST00000462622.5(DPP6):​n.46C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic,risk factor (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DPP6 ENST00000462622.5 non_coding_transcript_exon
• Clinical Significance: Pathogenic; risk factor no assertion criteria provided P:2 O:1
• Conservation: PhyloP100: 1.90
• Publications: 0 publications found

Genes affected

DPP6 (HGNC:3010): (dipeptidyl peptidase like 6) This gene encodes a single-pass type II membrane protein that is a member of the peptidase S9B family of serine proteases. This protein has no detectable protease activity, most likely due to the absence of the conserved serine residue normally present in the catalytic domain of serine proteases. However, it does bind specific voltage-gated potassium channels and alters their expression and biophysical properties. Variations in this gene may be associated with susceptibility to amyotrophic lateral sclerosis and with idiopathic ventricular fibrillation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

DPP6 Gene-Disease associations (from GenCC):

• autosomal dominant primary microcephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• paroxysmal familial ventricular fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, autosomal dominant 33

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• ventricular fibrillation, paroxysmal familial, 2

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000298417 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-154305155-C-T is Pathogenic according to our data. Variant chr7-154305155-C-T is described in ClinVar as Pathogenic|risk_factor. ClinVar VariationId is 16794.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000462622.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	NM_130797.4	MANE Select	c.244-141059C>T		intron	N/A	NP_570629.2
	DPP6	NM_001364497.2		c.61-141059C>T		intron	N/A	NP_001351426.1
	DPP6	NM_001364498.2		c.61-141059C>T		intron	N/A	NP_001351427.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	ENST00000462622.5	TSL:1	n.46C>T		non_coding_transcript_exon	Exon 1 of 3
	DPP6	ENST00000332007.7	TSL:1	c.-340C>T		5_prime_UTR	Exon 1 of 26	ENSP00000328226.3
	DPP6	ENST00000377770.8	TSL:1 MANE Select	c.244-141059C>T		intron	N/A	ENSP00000367001.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 609270 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 286652

African (AFR) AF: 0.00 AC: 0 AN: 11678

American (AMR) AF: 0.00 AC: 0 AN: 1386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4516

East Asian (EAS) AF: 0.00 AC: 0 AN: 4306

South Asian (SAS) AF: 0.00 AC: 0 AN: 12690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 551318

Other (OTH) AF: 0.00 AC: 0 AN: 20566

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic; risk factor

Submissions summary: Pathogenic:2 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Pathogenic:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

Clinical Genetics, Academic Medical Center

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

Ventricular fibrillation, paroxysmal familial, 2 Other:1

Apr 01, 2009

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.94
PhyloP100		1.9
PromoterAI		0.25	Neutral

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: rs606231226; hg19: chr7-154002240;