rs71534169

Variant names:

• chr7-154801156-T-G
• rs71534169
• NM_130797.4:c.1300-199T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_130797.4(DPP6):​c.1300-199T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.045 in 152,226 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.045 (209 hom., cov: 31)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.02
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-154801156-T-G is Benign according to our data. Variant chr7-154801156-T-G is described in ClinVar as Benign. ClinVar VariationId is 1244767.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_130797.4	c.1300-199T>G		intron_variant	Intron 12 of 25	ENST00000377770.8	NP_570629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770.8	c.1300-199T>G		intron_variant	Intron 12 of 25	1	NM_130797.4	ENSP00000367001.3

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6853 AN: 152108 Hom.: 209 Cov.: 31

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0254

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0281

Gnomad FIN AF: 0.0469

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0752

Gnomad OTH AF: 0.0397

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

GnomAD4 genome AF: 0.0450 AC: 6853 AN: 152226 Hom.: 209 Cov.: 31 AF XY: 0.0429 AC XY: 3191 AN XY: 74426

African (AFR) AF: 0.0121 AC: 501 AN: 41554

American (AMR) AF: 0.0254 AC: 388 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0281 AC: 135 AN: 4804

European-Finnish (FIN) AF: 0.0469 AC: 498 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0752 AC: 5111 AN: 67984

Other (OTH) AF: 0.0393 AC: 83 AN: 2114

Alfa AF: 0.0610 Hom.: 566

Bravo AF: 0.0415

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.14
DANN	Benign	0.44
PhyloP100		-2.0

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: rs71534169; hg19: chr7-154592866;