2-158826494-CATATATATATAT-CATATATATATATAT

Variant names:

• chr2-158826494-C-CAT
• rs750057852
• ENST00000343761.4:c.224+7_224+8insAT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000343761.4(DAPL1):​c.224+7_224+8insAT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0024 (8 hom., cov: 14)
  • Exomes 𝑓: 0.0043 (27 hom.)
• Consequence: DAPL1 ENST00000343761.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 8 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+7_224+8insAT		splice_region_variant, intron_variant	Intron 3 of 3	3		ENSP00000385306.2
DAPL1	ENST00000409042.5	c.299+7_299+8insAT		splice_region_variant, intron_variant	Intron 4 of 4	4		ENSP00000386422.1

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 144 AN: 60284 Hom.: 8 Cov.: 14

Gnomad AFR AF: 0.00175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.000621

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.00697

Gnomad FIN AF: 0.00191

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.00417

GnomAD4 exome AF: 0.00432 AC: 872 AN: 201624 Hom.: 27 Cov.: 1 AF XY: 0.00439 AC XY: 483 AN XY: 109934

Gnomad4 AFR exome AF: 0.00116

Gnomad4 AMR exome AF: 0.00233

Gnomad4 ASJ exome AF: 0.00319

Gnomad4 EAS exome AF: 0.00471

Gnomad4 SAS exome AF: 0.00806

Gnomad4 FIN exome AF: 0.0217

Gnomad4 NFE exome AF: 0.00181

Gnomad4 OTH exome AF: 0.00366

GnomAD4 genome AF: 0.00237 AC: 143 AN: 60326 Hom.: 8 Cov.: 14 AF XY: 0.00262 AC XY: 72 AN XY: 27512

Gnomad4 AFR AF: 0.00175

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.000621

Gnomad4 EAS AF: 0.0124

Gnomad4 SAS AF: 0.00701

Gnomad4 FIN AF: 0.00191

Gnomad4 NFE AF: 0.00140

Gnomad4 OTH AF: 0.00405

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;