Variant 2-158795377-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001017920.3(DAPL1):c.5C>A(p.Ala2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000238 in 1,555,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

DAPL1
NM_001017920.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.959

Variant links:

Genes affected

DAPL1 (HGNC:21490): (death associated protein like 1) Predicted to enable death domain binding activity. Predicted to be involved in apoptotic signaling pathway; cellular response to amino acid starvation; and negative regulation of autophagy. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

DAPL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21533582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAPL1	NM_001017920.3 linkuse as main transcript	c.5C>A	p.Ala2Glu	missense_variant	1/4	ENST00000309950.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DAPL1	ENST00000309950.8 linkuse as main transcript	c.5C>A	p.Ala2Glu	missense_variant	1/4	1	NM_001017920.3	P1
DAPL1	ENST00000621326.4 linkuse as main transcript	c.5C>A	p.Ala2Glu	missense_variant	1/5	1
DAPL1	ENST00000409042.5 linkuse as main transcript	c.5C>A	p.Ala2Glu	missense_variant	1/5	4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000235

AC:

AN:

1402934

Hom.:

Cov.:

AF XY:

0.0000202

AC XY:

AN XY:

692266

show subpopulations

Gnomad4 AFR exome

AF:

0.000565

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000277

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.000137

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2022

The c.5C>A (p.A2E) alteration is located in exon 1 (coding exon 1) of the DAPL1 gene. This alteration results from a C to A substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.020

T;.;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.55

T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.2

M;.;.

MutationTaster

Benign

0.76

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.1

N;.;N

REVEL

Benign

0.14

Sift

Uncertain

0.0060

D;.;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.74

P;.;.

Vest4

0.30

MutPred

0.22

Gain of solvent accessibility (P = 0.0261);Gain of solvent accessibility (P = 0.0261);Gain of solvent accessibility (P = 0.0261);

MVP

0.37

MPC

0.013

ClinPred

0.58

GERP RS

5.1

Varity_R

0.13

gMVP

0.16

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

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