rs887107

Variant names:

• chr7-153942476-T-C
• rs887107
• ENST00000404039.5:c.51+54742T>C

Variant summary

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

The NM_001364497.2(DPP6):​c.60+193468T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,108 control chromosomes in the GnomAD database, including 6,296 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 0.28 (6296 hom., cov: 34)
• Consequence: DPP6 NM_001364497.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 3 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

ENSG00000303399 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364497.2. 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_001364497.2		c.60+193468T>C		intron	N/A	NP_001351426.1
	DPP6	NM_001364498.2		c.60+193468T>C		intron	N/A	NP_001351427.1
	DPP6	NM_001364499.2		c.60+193468T>C		intron	N/A	NP_001351428.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	ENST00000404039.5	TSL:1	c.51+54742T>C		intron	N/A	ENSP00000385578.1
	DPP6	ENST00000706130.1		c.60+193468T>C		intron	N/A	ENSP00000516215.1
	ENSG00000303399	ENST00000794146.1		n.97+81T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42298 AN: 151990 Hom.: 6294 Cov.: 34

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.0860

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.278 AC: 42318 AN: 152108 Hom.: 6296 Cov.: 34 AF XY: 0.273 AC XY: 20301 AN XY: 74362

African (AFR) AF: 0.372 AC: 15417 AN: 41470

American (AMR) AF: 0.205 AC: 3130 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 834 AN: 3470

East Asian (EAS) AF: 0.0854 AC: 442 AN: 5176

South Asian (SAS) AF: 0.222 AC: 1072 AN: 4822

European-Finnish (FIN) AF: 0.251 AC: 2653 AN: 10578

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17891 AN: 68008

Other (OTH) AF: 0.273 AC: 577 AN: 2112

Alfa AF: 0.269 Hom.: 3153

Bravo AF: 0.279

Asia WGS AF: 0.159 AC: 558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.62
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs887107; hg19: chr7-153639561;