Genetic Variant DAPL1:p.Leu60Pro (chr2-158807087-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001017920.3(DAPL1):c.179T>C(p.Leu60Pro) variant causes a missense change. The variant allele was found at a frequency of 0.46 in 1,610,226 control chromosomes in the GnomAD database, including 177,071 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.49 ( 18774 hom., cov: 31)

Exomes 𝑓: 0.46 ( 158297 hom. )

Consequence

DAPL1
NM_001017920.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.14

Publications

35 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.931708E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAPL1	NM_001017920.3 link	c.179T>C	p.Leu60Pro	missense_variant	Exon 3 of 4	ENST00000309950.8	NP_001017920.2	A0PJW8M1E9T5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DAPL1	ENST00000309950.8 link	c.179T>C	p.Leu60Pro	missense_variant	Exon 3 of 4	1	NM_001017920.3	ENSP00000309538.4	A0PJW8
DAPL1	ENST00000621326.4 link	c.179T>C	p.Leu60Pro	missense_variant	Exon 3 of 5	1		ENSP00000479872.1	M1EA23
DAPL1	ENST00000343761.4 link	c.104T>C	p.Leu35Pro	missense_variant	Exon 2 of 4	3		ENSP00000385306.2	H0Y3U5
DAPL1	ENST00000409042.5 link	c.179T>C	p.Leu60Pro	missense_variant	Exon 3 of 5	4		ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes

AF:

0.489

AC:

74232

AN:

151902

Hom.:

18747

Cov.:

show subpopulations

Gnomad AFR

AF:

0.545

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.799

Gnomad SAS

AF:

0.583

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.447

GnomAD2 exomes

AF:

0.514

AC:

128436

AN:

250090

AF XY:

0.506

show subpopulations

Gnomad AFR exome

AF:

0.556

Gnomad AMR exome

AF:

0.694

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.795

Gnomad FIN exome

AF:

0.390

Gnomad NFE exome

AF:

0.426

Gnomad OTH exome

AF:

0.481

GnomAD4 exome

AF:

0.457

AC:

666751

AN:

1458206

Hom.:

158297

Cov.:

AF XY:

0.459

AC XY:

332638

AN XY:

725470

show subpopulations

African (AFR)

AF:

0.552

AC:

18430

AN:

33398

American (AMR)

AF:

0.681

AC:

30365

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

10626

AN:

26028

East Asian (EAS)

AF:

0.800

AC:

31673

AN:

39602

South Asian (SAS)

AF:

0.575

AC:

49317

AN:

85738

European-Finnish (FIN)

AF:

0.399

AC:

21249

AN:

53310

Middle Eastern (MID)

AF:

0.418

AC:

2404

AN:

5756

European-Non Finnish (NFE)

AF:

0.427

AC:

474219

AN:

1109574

Other (OTH)

AF:

0.473

AC:

28468

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

17136

34272

51407

68543

85679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14810

29620

44430

59240

74050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.489

AC:

74304

AN:

152020

Hom.:

18774

Cov.:

AF XY:

0.494

AC XY:

36683

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.545

AC:

22606

AN:

41462

American (AMR)

AF:

0.584

AC:

8931

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.411

AC:

1425

AN:

3466

East Asian (EAS)

AF:

0.800

AC:

4120

AN:

5148

South Asian (SAS)

AF:

0.583

AC:

2806

AN:

4812

European-Finnish (FIN)

AF:

0.400

AC:

4221

AN:

10552

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.423

AC:

28738

AN:

67972

Other (OTH)

AF:

0.447

AC:

944

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1915

3830

5745

7660

9575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.451

Hom.:

73228

Bravo

AF:

0.507

TwinsUK

AF:

0.420

AC:

1558

ALSPAC

AF:

0.430

AC:

1656

ESP6500AA

AF:

0.549

AC:

2420

ESP6500EA

AF:

0.434

AC:

3735

ExAC

AF:

0.507

AC:

61515

Asia WGS

AF:

0.630

AC:

2191

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0060

T;.;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.67

T;T;T

MetaRNN

Benign

0.0000029

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;.;.

PhyloP100

4.1

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.6

N;.;D

REVEL

Benign

0.068

Sift

Benign

0.045

D;.;D

Sift4G

Benign

0.16

T;D;D

Polyphen

0.76

P;.;.

Vest4

0.44

MPC

0.052

ClinPred

0.041

GERP RS

5.6

Varity_R

0.80

gMVP

0.25

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over