rs11243354

Variant names:

• chr7-154587524-T-C
• rs11243354
• ENST00000496611.2:c.*350T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001364502.2(DPP6):​c.*350T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,007,696 control chromosomes in the GnomAD database, including 23,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6990 hom., cov: 32)
  • Exomes 𝑓: 0.18 (16350 hom.)
• Consequence: DPP6 NM_001364502.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0380
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-154587524-T-C is Benign according to our data. Variant chr7-154587524-T-C is described in ClinVar as Benign. ClinVar VariationId is 1237202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364502.2. 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_130797.4	MANE Select	c.627+20608T>C		intron	N/A	NP_570629.2	P42658-1
	DPP6	NM_001364502.2		c.*350T>C		3_prime_UTR	Exon 6 of 6	NP_001351431.1	A0A994J521
	DPP6	NM_001364497.2		c.444+20608T>C		intron	N/A	NP_001351426.1	A0A994J7K0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	ENST00000496611.2	TSL:1	c.*350T>C		3_prime_UTR	Exon 6 of 6	ENSP00000516214.1	A0A994J521
	DPP6	ENST00000377770.8	TSL:1 MANE Select	c.627+20608T>C		intron	N/A	ENSP00000367001.3	P42658-1
	DPP6	ENST00000332007.7	TSL:1	c.441+20608T>C		intron	N/A	ENSP00000328226.3	P42658-2

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40351 AN: 151670 Hom.: 6969 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0853

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.184 AC: 157485 AN: 855908 Hom.: 16350 Cov.: 11 AF XY: 0.183 AC XY: 78904 AN XY: 431360

African (AFR) AF: 0.515 AC: 10742 AN: 20876

American (AMR) AF: 0.240 AC: 5841 AN: 24328

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 2470 AN: 16982

East Asian (EAS) AF: 0.0689 AC: 2277 AN: 33056

South Asian (SAS) AF: 0.166 AC: 9187 AN: 55302

European-Finnish (FIN) AF: 0.156 AC: 4736 AN: 30278

Middle Eastern (MID) AF: 0.165 AC: 725 AN: 4400

European-Non Finnish (NFE) AF: 0.180 AC: 113493 AN: 630992

Other (OTH) AF: 0.202 AC: 8014 AN: 39694

GnomAD4 genome AF: 0.266 AC: 40423 AN: 151788 Hom.: 6990 Cov.: 32 AF XY: 0.262 AC XY: 19434 AN XY: 74196

African (AFR) AF: 0.496 AC: 20490 AN: 41298

American (AMR) AF: 0.264 AC: 4024 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3466

East Asian (EAS) AF: 0.0851 AC: 436 AN: 5124

South Asian (SAS) AF: 0.154 AC: 740 AN: 4804

European-Finnish (FIN) AF: 0.147 AC: 1547 AN: 10548

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11974 AN: 67980

Other (OTH) AF: 0.231 AC: 487 AN: 2108

Alfa AF: 0.207 Hom.: 792

Bravo AF: 0.284

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.72
DANN	Benign	0.46
PhyloP100		0.038

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: rs11243354; hg19: chr7-154379234;