2-158826494-CATATATATATAT-CATATATATATATATATATATATATATATAT

Variant names:

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

Variant summary

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

The ENST00000343761.4(DAPL1):​c.224+7_224+8insATATATATATATATATAT variant causes a splice region, 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: 𝑓 0.011 (124 hom., cov: 14)
  • Exomes 𝑓: 0.0053 (251 hom.)
  • Failed GnomAD Quality Control
• 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+8insATATATATATATATATAT		splice_region intron	N/A	ENSP00000385306.2	H0Y3U5
	DAPL1	ENST00000409042.5	TSL:4	c.299+7_299+8insATATATATATATATATAT		splice_region intron	N/A	ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 677 AN: 60214 Hom.: 124 Cov.: 14

Gnomad AFR AF: 0.00254

Gnomad AMI AF: 0.0745

Gnomad AMR AF: 0.00666

Gnomad ASJ AF: 0.0237

Gnomad EAS AF: 0.000264

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.000954

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0182

Gnomad OTH AF: 0.0125

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00530 AC: 1067 AN: 201510 Hom.: 251 Cov.: 1 AF XY: 0.00561 AC XY: 616 AN XY: 109874

⚠️ 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: 0.000129 AC: 1 AN: 7742

Ashkenazi Jewish (ASJ) AF: 0.00239 AC: 12 AN: 5022

East Asian (EAS) AF: 0.00 AC: 0 AN: 12116

South Asian (SAS) AF: 0.000408 AC: 7 AN: 17140

European-Finnish (FIN) AF: 0.0395 AC: 669 AN: 16936

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

European-Non Finnish (NFE) AF: 0.00283 AC: 359 AN: 126784

Other (OTH) AF: 0.00211 AC: 19 AN: 9006

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0112 AC: 677 AN: 60256 Hom.: 124 Cov.: 14 AF XY: 0.00925 AC XY: 254 AN XY: 27468

African (AFR) AF: 0.00254 AC: 42 AN: 16558

American (AMR) AF: 0.00664 AC: 38 AN: 5720

Ashkenazi Jewish (ASJ) AF: 0.0237 AC: 38 AN: 1606

East Asian (EAS) AF: 0.000265 AC: 1 AN: 3778

South Asian (SAS) AF: 0.00502 AC: 10 AN: 1994

European-Finnish (FIN) AF: 0.000954 AC: 1 AN: 1048

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

European-Non Finnish (NFE) AF: 0.0182 AC: 517 AN: 28456

Other (OTH) AF: 0.0122 AC: 9 AN: 740

Alfa AF: 0.00255 Hom.: 71

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.092
Mutation Taster		=100/0	polymorphism

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; COSMIC: COSV59357540;