chr7-154052721-T-TT

Variant names:

• chr7-154052720-C-CT
• rs571183490
• NM_130797.4:c.-88dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_130797.4(DPP6):​c.-88dupT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.032 (81 hom., cov: 6)
  • Exomes 𝑓: 0.047 (11 hom.)
  • Failed GnomAD Quality Control
• Consequence: DPP6 NM_130797.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• 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

ENSG00000203335 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0315 (4460/141466) while in subpopulation NFE AF = 0.0474 (3082/64986). AF 95% confidence interval is 0.046. There are 81 homozygotes in GnomAd4. There are 2038 alleles in the male GnomAd4 subpopulation. Median coverage is 6. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4460 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.-88dupT		5_prime_UTR	Exon 1 of 26	NP_570629.2	P42658-1
	DPP6	NM_001290253.2		c.-88dupT		5_prime_UTR	Exon 1 of 6	NP_001277182.1	Q8IYG9
	DPP6	NM_001364497.2		c.60+303725dupT		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.-88dupT		5_prime_UTR	Exon 1 of 26	ENSP00000367001.3	P42658-1
	DPP6	ENST00000406326.5	TSL:1	c.-88dupT		5_prime_UTR	Exon 1 of 6	ENSP00000384393.1	Q8IYG9
	DPP6	ENST00000404039.5	TSL:1	c.51+164999dupT		intron	N/A	ENSP00000385578.1	E9PF59

Frequencies

GnomAD3 genomes AF: 0.0315 AC: 4461 AN: 141476 Hom.: 81 Cov.: 6

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.0574

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.0534

Gnomad EAS AF: 0.00171

Gnomad SAS AF: 0.0324

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.0448

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.0252

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0472 AC: 45935 AN: 973276 Hom.: 11 Cov.: 0 AF XY: 0.0470 AC XY: 22219 AN XY: 472752

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0133 AC: 233 AN: 17520

American (AMR) AF: 0.0256 AC: 358 AN: 14010

Ashkenazi Jewish (ASJ) AF: 0.0504 AC: 560 AN: 11112

East Asian (EAS) AF: 0.00967 AC: 101 AN: 10444

South Asian (SAS) AF: 0.0384 AC: 2093 AN: 54480

European-Finnish (FIN) AF: 0.0348 AC: 380 AN: 10928

Middle Eastern (MID) AF: 0.0476 AC: 124 AN: 2606

European-Non Finnish (NFE) AF: 0.0496 AC: 40558 AN: 818030

Other (OTH) AF: 0.0447 AC: 1528 AN: 34146

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0315 AC: 4460 AN: 141466 Hom.: 81 Cov.: 6 AF XY: 0.0298 AC XY: 2038 AN XY: 68400

African (AFR) AF: 0.0119 AC: 461 AN: 38752

American (AMR) AF: 0.0192 AC: 275 AN: 14354

Ashkenazi Jewish (ASJ) AF: 0.0534 AC: 180 AN: 3370

East Asian (EAS) AF: 0.00172 AC: 8 AN: 4648

South Asian (SAS) AF: 0.0326 AC: 144 AN: 4422

European-Finnish (FIN) AF: 0.0253 AC: 198 AN: 7824

Middle Eastern (MID) AF: 0.0455 AC: 12 AN: 264

European-Non Finnish (NFE) AF: 0.0474 AC: 3082 AN: 64986

Other (OTH) AF: 0.0250 AC: 49 AN: 1958

Alfa AF: 0.0125 Hom.: 121

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.093

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs571183490; hg19: chr7-153749805;