7-153852211-C-T

Variant names:

• chr7-153852211-C-T
• rs2192271
• NM_001364497.2:c.60+103203C>T

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+103203C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,172 control chromosomes in the GnomAD database, including 2,693 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 0.18 (2693 hom., cov: 32)
• Consequence: DPP6 NM_001364497.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 5 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
• ventricular fibrillation, paroxysmal familial, 2

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability, autosomal dominant 33

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	NM_001364497.2		c.60+103203C>T		intron	N/A	NP_001351426.1	A0A994J7K0
	DPP6	NM_001364498.2		c.60+103203C>T		intron	N/A	NP_001351427.1	A0A994J7K0
	DPP6	NM_001364499.2		c.60+103203C>T		intron	N/A	NP_001351428.1	A0A994J7K0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	ENST00000706130.1		c.60+103203C>T		intron	N/A	ENSP00000516215.1	A0A994J7K0

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28109 AN: 152054 Hom.: 2692 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.185 AC: 28130 AN: 152172 Hom.: 2693 Cov.: 32 AF XY: 0.181 AC XY: 13444 AN XY: 74404

African (AFR) AF: 0.149 AC: 6195 AN: 41508

American (AMR) AF: 0.169 AC: 2580 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3470

East Asian (EAS) AF: 0.152 AC: 785 AN: 5168

South Asian (SAS) AF: 0.247 AC: 1190 AN: 4826

European-Finnish (FIN) AF: 0.116 AC: 1225 AN: 10606

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14590 AN: 67998

Other (OTH) AF: 0.199 AC: 421 AN: 2116

Alfa AF: 0.205 Hom.: 9491

Bravo AF: 0.186

Asia WGS AF: 0.193 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.65
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs2192271; hg19: chr7-153549296;