Variant chr2-158807104-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001017920.3(DAPL1):c.196G>A(p.Ala66Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,607,762 control chromosomes in the GnomAD database, including 66,920 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.21 ( 4600 hom., cov: 32)

Exomes 𝑓: 0.28 ( 62320 hom. )

Consequence

DAPL1
NM_001017920.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.331

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004966527).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAPL1	NM_001017920.3 linkuse as main transcript	c.196G>A	p.Ala66Thr	missense_variant	3/4	ENST00000309950.8	NP_001017920.2	A0PJW8M1E9T5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DAPL1	ENST00000309950.8 linkuse as main transcript	c.196G>A	p.Ala66Thr	missense_variant	3/4	1	NM_001017920.3	ENSP00000309538.4	A0PJW8
DAPL1	ENST00000621326.4 linkuse as main transcript	c.196G>A	p.Ala66Thr	missense_variant	3/5	1		ENSP00000479872.1	M1EA23
DAPL1	ENST00000343761.4 linkuse as main transcript	c.121G>A	p.Ala41Thr	missense_variant	2/4	3		ENSP00000385306.2	H0Y3U5
DAPL1	ENST00000409042.5 linkuse as main transcript	c.196G>A	p.Ala66Thr	missense_variant	3/5	4		ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32688

AN:

152012

Hom.:

4600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0549

Gnomad AMI

AF:

0.426

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.0264

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.232

GnomAD3 exomes

AF:

0.225

AC:

56285

AN:

249660

Hom.:

7948

AF XY:

0.230

AC XY:

31096

AN XY:

134992

show subpopulations

Gnomad AFR exome

AF:

0.0463

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.0214

Gnomad SAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.326

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.252

GnomAD4 exome

AF:

0.280

AC:

408091

AN:

1455632

Hom.:

62320

Cov.:

AF XY:

0.278

AC XY:

201371

AN XY:

724230

show subpopulations

Gnomad4 AFR exome

AF:

0.0441

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.262

Gnomad4 EAS exome

AF:

0.0148

Gnomad4 SAS exome

AF:

0.141

Gnomad4 FIN exome

AF:

0.316

Gnomad4 NFE exome

AF:

0.314

Gnomad4 OTH exome

AF:

0.255

GnomAD4 genome

AF:

0.215

AC:

32680

AN:

152130

Hom.:

4600

Cov.:

AF XY:

0.212

AC XY:

15749

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0548

Gnomad4 AMR

AF:

0.174

Gnomad4 ASJ

AF:

0.266

Gnomad4 EAS

AF:

0.0263

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.320

Gnomad4 NFE

AF:

0.320

Gnomad4 OTH

AF:

0.232

Alfa

AF:

0.283

Hom.:

13401

Bravo

AF:

0.195

TwinsUK

AF:

0.305

AC:

1132

ALSPAC

AF:

0.307

AC:

1182

ESP6500AA

AF:

0.0581

AC:

256

ESP6500EA

AF:

0.303

AC:

2604

ExAC

AF:

0.227

AC:

27541

Asia WGS

AF:

0.0940

AC:

325

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.9

DANN

Benign

0.61

DEOGEN2

Benign

0.011

T;.;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.49

T;T;T

MetaRNN

Benign

0.0050

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.86

N;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.11

N;.;N

REVEL

Benign

0.033

Sift

Benign

1.0

T;.;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.070

MPC

0.012

ClinPred

0.00034

GERP RS

1.9

Varity_R

0.029

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over