chr7-154361389-C-T

Variant names:

• chr7-154361389-C-T
• rs12536378
• NM_130797.4:c.244-84825C>T

Variant summary

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

The NM_130797.4(DPP6):​c.244-84825C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,996 control chromosomes in the GnomAD database, including 21,880 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 0.50 (21880 hom., cov: 32)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573
• Publications: 6 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130797.4. 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.244-84825C>T		intron	N/A	NP_570629.2
	DPP6	NM_001364497.2		c.61-84825C>T		intron	N/A	NP_001351426.1
	DPP6	NM_001364498.2		c.61-84825C>T		intron	N/A	NP_001351427.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	ENST00000377770.8	TSL:1 MANE Select	c.244-84825C>T		intron	N/A	ENSP00000367001.3
	DPP6	ENST00000332007.7	TSL:1	c.57+55838C>T		intron	N/A	ENSP00000328226.3
	DPP6	ENST00000404039.5	TSL:1	c.52-84825C>T		intron	N/A	ENSP00000385578.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75643 AN: 151878 Hom.: 21883 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.498 AC: 75643 AN: 151996 Hom.: 21880 Cov.: 32 AF XY: 0.506 AC XY: 37587 AN XY: 74298

African (AFR) AF: 0.185 AC: 7651 AN: 41452

American (AMR) AF: 0.605 AC: 9247 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1968 AN: 3472

East Asian (EAS) AF: 0.714 AC: 3679 AN: 5152

South Asian (SAS) AF: 0.535 AC: 2571 AN: 4810

European-Finnish (FIN) AF: 0.678 AC: 7160 AN: 10558

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41412 AN: 67962

Other (OTH) AF: 0.522 AC: 1103 AN: 2112

Alfa AF: 0.550 Hom.: 47095

Bravo AF: 0.478

Asia WGS AF: 0.574 AC: 1995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.79
PhyloP100		0.57

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: rs12536378; hg19: chr7-154058474;