2-158826494-CATATATATATAT-CATATATATATATATAT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000343761.4(DAPL1):​c.224+7_224+8insATAT 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 0.00015 (0 hom., cov: 14)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: DAPL1 ENST00000343761.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000343761.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAPL1	ENST00000343761.4	TSL:3	c.224+7_224+8insATAT		splice_region intron	N/A	ENSP00000385306.2	H0Y3U5
	DAPL1	ENST00000409042.5	TSL:4	c.299+7_299+8insATAT		splice_region intron	N/A	ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes AF: 0.000149 AC: 9 AN: 60294 Hom.: 0 Cov.: 14

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00158

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000351

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000168 AC: 34 AN: 201810 Hom.: 1 Cov.: 1 AF XY: 0.000155 AC XY: 17 AN XY: 110010

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 6034

American (AMR) AF: 0.00 AC: 0 AN: 7742

Ashkenazi Jewish (ASJ) AF: 0.000199 AC: 1 AN: 5024

East Asian (EAS) AF: 0.0000825 AC: 1 AN: 12116

South Asian (SAS) AF: 0.000408 AC: 7 AN: 17138

European-Finnish (FIN) AF: 0.000697 AC: 12 AN: 17226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 730

European-Non Finnish (NFE) AF: 0.000103 AC: 13 AN: 126792

Other (OTH) AF: 0.00 AC: 0 AN: 9008

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000144382), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000149 AC: 9 AN: 60336 Hom.: 0 Cov.: 14 AF XY: 0.000218 AC XY: 6 AN XY: 27516

African (AFR) AF: 0.000121 AC: 2 AN: 16572

American (AMR) AF: 0.00 AC: 0 AN: 5720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1610

East Asian (EAS) AF: 0.00159 AC: 6 AN: 3778

South Asian (SAS) AF: 0.00 AC: 0 AN: 1996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 74

European-Non Finnish (NFE) AF: 0.0000351 AC: 1 AN: 28516

Other (OTH) AF: 0.00 AC: 0 AN: 740

Alfa AF: 0.00 Hom.: 71

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.092

Splicing

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

Other links and lift over

dbSNP: rs750057852; hg19: chr2-159683006;