rs528815814

Variant names:

• chr7-154052919-C-G
• rs528815814
• NM_130797.4:c.99C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-154052919-C-G
• chr7-154052919-C-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_130797.4(DPP6):​c.99C>G​(p.Pro33Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000447 in 1,496,680 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00045 (1 hom.)
• Consequence: DPP6 NM_130797.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.19
• Publications: 0 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

ENSG00000203335 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 7-154052919-C-G is Benign according to our data. Variant chr7-154052919-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2658247.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.19 with no splicing effect.
• BS2: High AC in GnomAd4 at 68 AD,Unknown gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	NM_130797.4	MANE Select	c.99C>G	p.Pro33Pro	synonymous	Exon 1 of 26	NP_570629.2	P42658-1
	DPP6	NM_001290253.2		c.99C>G	p.Pro33Pro	synonymous	Exon 1 of 6	NP_001277182.1	Q8IYG9
	DPP6	NM_001364497.2		c.60+303911C>G		intron	N/A	NP_001351426.1	A0A994J7K0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	ENST00000377770.8	TSL:1 MANE Select	c.99C>G	p.Pro33Pro	synonymous	Exon 1 of 26	ENSP00000367001.3	P42658-1
	DPP6	ENST00000406326.5	TSL:1	c.99C>G	p.Pro33Pro	synonymous	Exon 1 of 6	ENSP00000384393.1	Q8IYG9
	DPP6	ENST00000404039.5	TSL:1	c.51+165185C>G		intron	N/A	ENSP00000385578.1	E9PF59

Frequencies

GnomAD3 genomes AF: 0.000454 AC: 68 AN: 149632 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000267

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000419

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000743

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000446 AC: 55 AN: 123186 AF XY: 0.000488

Gnomad AFR exome AF: 0.000232

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000389

Gnomad NFE exome AF: 0.000913

Gnomad OTH exome AF: 0.000545

GnomAD4 exome AF: 0.000446 AC: 601 AN: 1346944 Hom.: 1 Cov.: 44 AF XY: 0.000463 AC XY: 308 AN XY: 664774

African (AFR) AF: 0.0000346 AC: 1 AN: 28874

American (AMR) AF: 0.000265 AC: 9 AN: 33960

Ashkenazi Jewish (ASJ) AF: 0.0000423 AC: 1 AN: 23640

East Asian (EAS) AF: 0.00 AC: 0 AN: 31820

South Asian (SAS) AF: 0.0000256 AC: 2 AN: 78060

European-Finnish (FIN) AF: 0.000340 AC: 12 AN: 35326

Middle Eastern (MID) AF: 0.000206 AC: 1 AN: 4858

European-Non Finnish (NFE) AF: 0.000522 AC: 551 AN: 1055126

Other (OTH) AF: 0.000434 AC: 24 AN: 55280

GnomAD4 genome AF: 0.000454 AC: 68 AN: 149736 Hom.: 0 Cov.: 31 AF XY: 0.000328 AC XY: 24 AN XY: 73120

African (AFR) AF: 0.000243 AC: 10 AN: 41236

American (AMR) AF: 0.000266 AC: 4 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 5082

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000419 AC: 4 AN: 9540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000743 AC: 50 AN: 67306

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000467 Hom.: 0

Bravo AF: 0.000544

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.71
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs528815814; hg19: chr7-153750004;