7-153881331-A-G

Variant names:

• chr7-153881331-A-G
• rs38989
• NM_001364497.2:c.60+132323A>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+132323A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,106 control chromosomes in the GnomAD database, including 11,304 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 0.38 (11304 hom., cov: 33)
• Consequence: DPP6 NM_001364497.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_001364497.2	c.60+132323A>G		intron_variant	Intron 2 of 26		NP_001351426.1
DPP6	NM_001364498.2	c.60+132323A>G		intron_variant	Intron 2 of 26		NP_001351427.1
DPP6	NM_001364499.2	c.60+132323A>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+132323A>G		intron_variant	Intron 2 of 26			ENSP00000516215.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57982 AN: 151988 Hom.: 11301 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.381 AC: 58012 AN: 152106 Hom.: 11304 Cov.: 33 AF XY: 0.374 AC XY: 27812 AN XY: 74352

African (AFR) AF: 0.315 AC: 13065 AN: 41484

American (AMR) AF: 0.388 AC: 5935 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1367 AN: 3466

East Asian (EAS) AF: 0.286 AC: 1478 AN: 5172

South Asian (SAS) AF: 0.389 AC: 1879 AN: 4828

European-Finnish (FIN) AF: 0.279 AC: 2949 AN: 10582

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29818 AN: 67964

Other (OTH) AF: 0.404 AC: 854 AN: 2112

Alfa AF: 0.386 Hom.: 6715

Bravo AF: 0.385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.38
PhyloP100		-0.55

Splicing

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

Other links and lift over

dbSNP: rs38989; hg19: chr7-153578416;