7-153838604-C-G

Variant names:

• chr7-153838604-C-G
• rs2110267
• NM_001364497.2:c.60+89596C>G

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+89596C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,906 control chromosomes in the GnomAD database, including 9,139 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 0.32 (9139 hom., cov: 32)
• Consequence: DPP6 NM_001364497.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 7 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_001364497.2	c.60+89596C>G		intron_variant	Intron 2 of 26		NP_001351426.1
DPP6	NM_001364498.2	c.60+89596C>G		intron_variant	Intron 2 of 26		NP_001351427.1
DPP6	NM_001364499.2	c.60+89596C>G		intron_variant	Intron 2 of 26		NP_001351428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000706130.1	c.60+89596C>G		intron_variant	Intron 2 of 26			ENSP00000516215.1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49018 AN: 151786 Hom.: 9115 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.323 AC: 49084 AN: 151906 Hom.: 9139 Cov.: 32 AF XY: 0.319 AC XY: 23724 AN XY: 74256

African (AFR) AF: 0.507 AC: 20984 AN: 41374

American (AMR) AF: 0.232 AC: 3540 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3470

East Asian (EAS) AF: 0.404 AC: 2083 AN: 5156

South Asian (SAS) AF: 0.456 AC: 2194 AN: 4810

European-Finnish (FIN) AF: 0.163 AC: 1718 AN: 10542

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16664 AN: 67950

Other (OTH) AF: 0.310 AC: 655 AN: 2112

Alfa AF: 0.275 Hom.: 814

Bravo AF: 0.334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.66
DANN	Benign	0.34
PhyloP100		0.025

Splicing

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

Other links and lift over

dbSNP: rs2110267; hg19: chr7-153535689;