Variant 2-158815811-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001017920.3(DAPL1):c.314G>A(p.Arg105Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000429 in 1,609,924 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

DAPL1
NM_001017920.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.39

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAPL1	NM_001017920.3 link	c.314G>A	p.Arg105Gln	missense_variant	4/4	ENST00000309950.8	NP_001017920.2	A0PJW8M1E9T5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DAPL1	ENST00000309950.8 link	c.314G>A	p.Arg105Gln	missense_variant	4/4	1	NM_001017920.3	ENSP00000309538.4	A0PJW8
DAPL1	ENST00000621326.4 link	c.*28G>A		3_prime_UTR_variant	5/5	1		ENSP00000479872.1	M1EA23
DAPL1	ENST00000343761.4 link	c.132+8696G>A		intron_variant		3		ENSP00000385306.2	H0Y3U5
DAPL1	ENST00000409042.5 link	c.207+8696G>A		intron_variant		4		ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000636

AC:

AN:

251414

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135884

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000453

AC:

AN:

1457740

Hom.:

Cov.:

AF XY:

0.0000469

AC XY:

AN XY:

725542

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000496

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000947

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

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

May 24, 2023

The c.314G>A (p.R105Q) alteration is located in exon 4 (coding exon 4) of the DAPL1 gene. This alteration results from a G to A substitution at nucleotide position 314, causing the arginine (R) at amino acid position 105 to be replaced by a glutamine (Q). 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

0.16

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.85

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.89

MutationAssessor

Pathogenic

3.1

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.26

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.012

Polyphen

0.32

Vest4

0.81

MutPred

0.61

Loss of MoRF binding (P = 0.0093);

MVP

0.16

MPC

0.091

ClinPred

0.88

GERP RS

3.8

Varity_R

0.50

gMVP

0.60

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