ENST00000343761.4:c.224+2_224+3insTATATATATATATATATATA

Variant names:

• chr2-158826488-G-GTATATATATATATATATATA
• ENST00000343761.4:c.224+1_224+2insTATATATATATATATATATA

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Strong

The ENST00000343761.4(DAPL1):​c.224+1_224+2insTATATATATATATATATATA variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 18)
• Consequence: DAPL1 ENST00000343761.4 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.351
• 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 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.17590822 fraction of the gene. Cryptic splice site detected, with MaxEntScore 7.8, offset of 0 (no position change), new splice context is: aagGTatat. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

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+1_224+2insTATATATATATATATATATA		splice_donor intron	N/A	ENSP00000385306.2	H0Y3U5
	DAPL1	ENST00000409042.5	TSL:4	c.299+1_299+2insTATATATATATATATATATA		splice_donor intron	N/A	ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Cov.: 12

GnomAD4 genome Cov.: 18

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35

Splicing

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

Other links and lift over

hg19: chr2-159683000;