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

Variant names:

• chr2-158826488-G-GTATATATATATATATATATATATATATATA
• ENST00000343761.4:c.224+1_224+2insTATATATATATATATATATATATATATATA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Strong

The ENST00000343761.4(DAPL1):​c.224+1_224+2insTATATATATATATATATATATATATATATA variant causes a splice donor, 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: not found (cov: 18)
• Consequence: DAPL1 ENST00000343761.4 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.351

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 Uncertain_significance. Variant got 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.

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+1_224+2insTATATATATATATATATATATATATATATA		splice_donor_variant, intron_variant	Intron 3 of 3	3		ENSP00000385306.2
DAPL1	ENST00000409042.5	c.299+1_299+2insTATATATATATATATATATATATATATATA		splice_donor_variant, intron_variant	Intron 4 of 4	4		ENSP00000386422.1

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Cov.: 12

GnomAD4 genome Cov.: 18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-159683000;