dbSNP rs17810398: DAPL1:p.Phe45Leu (chr2-158804358-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001017920.3(DAPL1):c.135C>A(p.Phe45Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DAPL1
NM_001017920.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0260

Publications

10 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015643775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAPL1	NM_001017920.3 link	c.135C>A	p.Phe45Leu	missense_variant	Exon 2 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.135C>A	p.Phe45Leu	missense_variant	Exon 2 of 4	1	NM_001017920.3	ENSP00000309538.4	A0PJW8
DAPL1	ENST00000621326.4 link	c.135C>A	p.Phe45Leu	missense_variant	Exon 2 of 5	1		ENSP00000479872.1	M1EA23
DAPL1	ENST00000343761.4 link	c.60C>A	p.Phe20Leu	missense_variant	Exon 1 of 4	3		ENSP00000385306.2	H0Y3U5
DAPL1	ENST00000409042.5 link	c.135C>A	p.Phe45Leu	missense_variant	Exon 2 of 5	4		ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

243370

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456200

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724086

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33300

American (AMR)

AF:

0.00

AC:

AN:

44174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25924

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

85368

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1108700

Other (OTH)

AF:

0.00

AC:

AN:

60138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

1899

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.57

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.0017

T;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.52

T;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.2

N;.;.

PhyloP100

-0.026

PrimateAI

Benign

0.31

PROVEAN

Benign

0.74

N;.;N

REVEL

Benign

0.039

Sift

Benign

0.78

T;.;T

Sift4G

Benign

0.36

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.053

MutPred

0.29

Gain of ubiquitination at K42 (P = 0.07);Gain of ubiquitination at K42 (P = 0.07);Gain of ubiquitination at K42 (P = 0.07);

MVP

0.030

MPC

0.012

ClinPred

0.052

GERP RS

-5.9

PromoterAI

-0.11

Neutral

(source)

Varity_R

0.063

gMVP

0.070

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over