Genetic Variant DNPEP:c.937-6C>T (chr2-219382145-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_012100.4(DNPEP):c.937-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,607,552 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0086 ( 16 hom., cov: 33)

Exomes 𝑓: 0.00096 ( 15 hom. )

Consequence

DNPEP
NM_012100.4 splice_region, intron

Scores

Splicing: ADA: 0.00009287

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.129

Variant links:

Genes affected

DNPEP (HGNC:2981): (aspartyl aminopeptidase) The protein encoded by this gene is an aminopeptidase which prefers acidic amino acids, and specifically favors aspartic acid over glutamic acid. It is thought to be a cytosolic protein involved in general metabolism of intracellular proteins. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

DNPEP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 2-219382145-G-A is Benign according to our data. Variant chr2-219382145-G-A is described in ClinVar as [Benign]. Clinvar id is 775822.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00858 (1307/152334) while in subpopulation AFR AF= 0.0293 (1220/41570). AF 95% confidence interval is 0.028. There are 16 homozygotes in gnomad4. There are 612 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNPEP	NM_012100.4 link	c.937-6C>T		splice_region_variant, intron_variant	Intron 10 of 14	ENST00000273075.9	NP_036232.2	Q9ULA0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNPEP	ENST00000273075.9 link	c.937-6C>T		splice_region_variant, intron_variant	Intron 10 of 14	1	NM_012100.4	ENSP00000273075.4		Q9ULA0-1

Frequencies

GnomAD3 genomes

AF:

0.00857

AC:

1304

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0294

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00220

AC:

535

AN:

243166

Hom.:

AF XY:

0.00159

AC XY:

211

AN XY:

132330

show subpopulations

Gnomad AFR exome

AF:

0.0293

Gnomad AMR exome

AF:

0.00186

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000981

Gnomad OTH exome

AF:

0.00134

GnomAD4 exome

AF:

0.000962

AC:

1400

AN:

1455218

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

603

AN XY:

724098

show subpopulations

Gnomad4 AFR exome

AF:

0.0324

Gnomad4 AMR exome

AF:

0.00206

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000666

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00858

AC:

1307

AN:

152334

Hom.:

Cov.:

AF XY:

0.00822

AC XY:

612

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0293

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00422

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.1

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000093

dbscSNV1_RF

Benign

0.030

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over