2-158826494-CATATATATATAT-CATATATATAT

Variant names:

• chr2-158826494-CAT-C
• rs750057852
• ENST00000343761.4:c.224+8_224+9delAT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000343761.4(DAPL1):​c.224+8_224+9delAT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 261,732 control chromosomes in the GnomAD database, including 631 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0092 (41 hom., cov: 14)
  • Exomes 𝑓: 0.030 (590 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.03 (6043/201402) while in subpopulation SAS AF= 0.0304 (521/17112). AF 95% confidence interval is 0.0283. There are 590 homozygotes in gnomad4_exome. There are 3215 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 41 AR gene

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+9delAT		splice_region_variant, intron_variant	Intron 3 of 3	3		ENSP00000385306.2
DAPL1	ENST00000409042.5	c.299+8_299+9delAT		splice_region_variant, intron_variant	Intron 4 of 4	4		ENSP00000386422.1

Frequencies

GnomAD3 genomes AF: 0.00911 AC: 549 AN: 60288 Hom.: 40 Cov.: 14

Gnomad AFR AF: 0.00248

Gnomad AMI AF: 0.00355

Gnomad AMR AF: 0.00929

Gnomad ASJ AF: 0.00683

Gnomad EAS AF: 0.0103

Gnomad SAS AF: 0.0189

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0111

GnomAD4 exome AF: 0.0300 AC: 6043 AN: 201402 Hom.: 590 AF XY: 0.0293 AC XY: 3215 AN XY: 109778

Gnomad4 AFR exome AF: 0.00315

Gnomad4 AMR exome AF: 0.0193

Gnomad4 ASJ exome AF: 0.0231

Gnomad4 EAS exome AF: 0.00901

Gnomad4 SAS exome AF: 0.0304

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.0170

Gnomad4 OTH exome AF: 0.0147

GnomAD4 genome AF: 0.00917 AC: 553 AN: 60330 Hom.: 41 Cov.: 14 AF XY: 0.00942 AC XY: 259 AN XY: 27506

Gnomad4 AFR AF: 0.00253

Gnomad4 AMR AF: 0.00962

Gnomad4 ASJ AF: 0.00683

Gnomad4 EAS AF: 0.0103

Gnomad4 SAS AF: 0.0186

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.0120

Gnomad4 OTH AF: 0.0135

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;