2-158826494-CATATATATATAT-CATATATATATATATATATATATATATATATAT

Variant names:

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

Variant summary

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

The ENST00000343761.4(DAPL1):​c.224+7_224+8insATATATATATATATATATAT 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 0.026 (325 hom., cov: 14)
  • Exomes 𝑓: 0.0076 (369 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.026 (1564/60118) while in subpopulation NFE AF= 0.0453 (1285/28370). AF 95% confidence interval is 0.0432. There are 325 homozygotes in gnomad4. There are 614 alleles in male gnomad4 subpopulation. Median coverage is 14. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 325 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+8insATATATATATATATATATAT		splice_region_variant, intron_variant	Intron 3 of 3	3		ENSP00000385306.2
DAPL1	ENST00000409042.5	c.299+7_299+8insATATATATATATATATATAT		splice_region_variant, intron_variant	Intron 4 of 4	4		ENSP00000386422.1

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 1564 AN: 60076 Hom.: 325 Cov.: 14

Gnomad AFR AF: 0.00642

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.00985

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00106

Gnomad SAS AF: 0.00747

Gnomad FIN AF: 0.0115

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0453

Gnomad OTH AF: 0.0195

GnomAD4 exome AF: 0.00765 AC: 1540 AN: 201360 Hom.: 369 Cov.: 1 AF XY: 0.00746 AC XY: 819 AN XY: 109790

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000387

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000175

Gnomad4 FIN exome AF: 0.0733

Gnomad4 NFE exome AF: 0.00225

Gnomad4 OTH exome AF: 0.00200

GnomAD4 genome AF: 0.0260 AC: 1564 AN: 60118 Hom.: 325 Cov.: 14 AF XY: 0.0224 AC XY: 614 AN XY: 27414

Gnomad4 AFR AF: 0.00641

Gnomad4 AMR AF: 0.00982

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.00106

Gnomad4 SAS AF: 0.00752

Gnomad4 FIN AF: 0.0115

Gnomad4 NFE AF: 0.0453

Gnomad4 OTH AF: 0.0190

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;