Genetic Variant DAPL1:c.224+8_224+11delATAT (chr2-158826494-CATAT-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The ENST00000343761.4(DAPL1):c.224+8_224+11delATAT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000423 in 262,132 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 14)

Exomes 𝑓: 0.00045 ( 1 hom. )

Consequence

DAPL1
ENST00000343761.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.730

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:

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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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAPL1	ENST00000343761.4 link	c.224+8_224+11delATAT		splice_region_variant, intron_variant	Intron 3 of 3	3		ENSP00000385306.2		H0Y3U5
DAPL1	ENST00000409042.5 link	c.299+8_299+11delATAT		splice_region_variant, intron_variant	Intron 4 of 4	4		ENSP00000386422.1		B8ZZC6

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

60296

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000351

Gnomad ASJ

AF:

0.00248

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000498

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0128

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000446

AC:

AN:

201794

Hom.:

AF XY:

0.000500

AC XY:

AN XY:

110006

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000129

Gnomad4 ASJ exome

AF:

0.00498

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000700

Gnomad4 FIN exome

AF:

0.000290

Gnomad4 NFE exome

AF:

0.000355

Gnomad4 OTH exome

AF:

0.000111

GnomAD4 genome

AF:

0.000348

AC:

AN:

60338

Hom.:

Cov.:

AF XY:

0.000327

AC XY:

AN XY:

27516

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000350

Gnomad4 ASJ

AF:

0.00248

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000501

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

2-158826494-CATATATATATAT-CATATATAT

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