chr2-158826494-CATAT-C

Variant names:

• chr2-158826494-CATAT-C
• rs750057852
• ENST00000343761.4:c.224+8_224+11delATAT

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730

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]

ACMG classification

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	c.224+8_224+11delATAT		splice_region_variant, intron_variant	Intron 3 of 3	3		ENSP00000385306.2
DAPL1	ENST00000409042.5	c.299+8_299+11delATAT		splice_region_variant, intron_variant	Intron 4 of 4	4		ENSP00000386422.1

Frequencies

GnomAD3 genomes AF: 0.000348 AC: 21 AN: 60296 Hom.: 0 Cov.: 14

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: 90 AN: 201794 Hom.: 1 AF XY: 0.000500 AC XY: 55 AN XY: 110006

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: 21 AN: 60338 Hom.: 0 Cov.: 14 AF XY: 0.000327 AC XY: 9 AN XY: 27516

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs750057852; hg19: chr2-159683006;