rs3807218

Variant names:

• chr7-154669402-A-G
• rs3807218
• NM_130797.4:c.723A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-154669402-A-G
• chr7-154669402-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_130797.4(DPP6):​c.723A>G​(p.Lys241Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 1,556,854 control chromosomes in the GnomAD database, including 615,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52939 hom., cov: 33)
  • Exomes 𝑓: 0.89 (562280 hom.)
• Consequence: DPP6 NM_130797.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.500
• Publications: 26 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 7-154669402-A-G is Benign according to our data. Variant chr7-154669402-A-G is described in ClinVar as Benign. ClinVar VariationId is 1174770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.5 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130797.4. 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_130797.4	MANE Select	c.723A>G	p.Lys241Lys	synonymous	Exon 7 of 26	NP_570629.2
	DPP6	NM_001364497.2		c.540A>G	p.Lys180Lys	synonymous	Exon 8 of 27	NP_001351426.1
	DPP6	NM_001364498.2		c.540A>G	p.Lys180Lys	synonymous	Exon 8 of 27	NP_001351427.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	ENST00000377770.8	TSL:1 MANE Select	c.723A>G	p.Lys241Lys	synonymous	Exon 7 of 26	ENSP00000367001.3
	DPP6	ENST00000332007.7	TSL:1	c.537A>G	p.Lys179Lys	synonymous	Exon 7 of 26	ENSP00000328226.3
	DPP6	ENST00000404039.5	TSL:1	c.531A>G	p.Lys177Lys	synonymous	Exon 7 of 26	ENSP00000385578.1

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125976 AN: 152086 Hom.: 52918 Cov.: 33

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.830

GnomAD2 exomes AF: 0.869 AC: 145053 AN: 166836 AF XY: 0.875

Gnomad AFR exome AF: 0.666

Gnomad AMR exome AF: 0.846

Gnomad ASJ exome AF: 0.848

Gnomad EAS exome AF: 0.847

Gnomad FIN exome AF: 0.892

Gnomad NFE exome AF: 0.905

Gnomad OTH exome AF: 0.882

GnomAD4 exome AF: 0.894 AC: 1255315 AN: 1404650 Hom.: 562280 Cov.: 67 AF XY: 0.893 AC XY: 619288 AN XY: 693224

African (AFR) AF: 0.665 AC: 21245 AN: 31940

American (AMR) AF: 0.845 AC: 30659 AN: 36272

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 21331 AN: 25230

East Asian (EAS) AF: 0.851 AC: 30992 AN: 36416

South Asian (SAS) AF: 0.871 AC: 69227 AN: 79452

European-Finnish (FIN) AF: 0.898 AC: 44697 AN: 49790

Middle Eastern (MID) AF: 0.870 AC: 4961 AN: 5704

European-Non Finnish (NFE) AF: 0.907 AC: 981124 AN: 1081576

Other (OTH) AF: 0.877 AC: 51079 AN: 58270

GnomAD4 genome AF: 0.828 AC: 126041 AN: 152204 Hom.: 52939 Cov.: 33 AF XY: 0.828 AC XY: 61647 AN XY: 74426

African (AFR) AF: 0.670 AC: 27788 AN: 41490

American (AMR) AF: 0.842 AC: 12882 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2946 AN: 3472

East Asian (EAS) AF: 0.842 AC: 4362 AN: 5178

South Asian (SAS) AF: 0.851 AC: 4099 AN: 4816

European-Finnish (FIN) AF: 0.901 AC: 9548 AN: 10602

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61584 AN: 68022

Other (OTH) AF: 0.827 AC: 1749 AN: 2114

Alfa AF: 0.881 Hom.: 267142

Bravo AF: 0.819

Asia WGS AF: 0.813 AC: 2828 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Ventricular fibrillation, paroxysmal familial, 2;C4225375:Intellectual disability, autosomal dominant 33 Benign:1

Aug 11, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.2
DANN	Benign	0.53
PhyloP100		-0.50

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: rs3807218; hg19: chr7-154461112; COSMIC: COSV108116168;