Genetic Variant DAPL1:c.224+7_224+8insATATATATATATAT (chr2-158826494-C-CATATATATATATAT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The ENST00000343761.4(DAPL1):c.224+7_224+8insATATATATATATAT 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 0.00050 ( 1 hom., cov: 14)

Exomes 𝑓: 0.00083 ( 30 hom. )

Failed GnomAD Quality Control

Consequence

DAPL1
ENST00000343761.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0920

Publications

0 publications found

Variant links:

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]

DAPL1 links:

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ACMG classification

Classification was made for transcript

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+8insATATATATATATAT		splice_region intron	N/A	ENSP00000385306.2	H0Y3U5
	DAPL1	ENST00000409042.5	TSL:4	c.299+7_299+8insATATATATATATAT		splice_region intron	N/A	ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes

AF:

0.000498

AC:

AN:

60286

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000175

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000281

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000828

AC:

167

AN:

201792

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

109998

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

6034

American (AMR)

AF:

0.000258

AC:

AN:

7742

Ashkenazi Jewish (ASJ)

AF:

0.000796

AC:

AN:

5024

East Asian (EAS)

AF:

0.00

AC:

AN:

12116

South Asian (SAS)

AF:

0.000117

AC:

AN:

17140

European-Finnish (FIN)

AF:

0.00640

AC:

110

AN:

17200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

730

European-Non Finnish (NFE)

AF:

0.000371

AC:

AN:

126796

Other (OTH)

AF:

0.000222

AC:

AN:

9010

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000555111), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.395

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000497

AC:

AN:

60328

Hom.:

Cov.:

AF XY:

0.000582

AC XY:

AN XY:

27512

show subpopulations

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

African (AFR)

AF:

0.00127

AC:

AN:

16568

American (AMR)

AF:

0.000175

AC:

AN:

5720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1610

East Asian (EAS)

AF:

0.00

AC:

AN:

3778

South Asian (SAS)

AF:

0.00

AC:

AN:

1996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000281

AC:

AN:

28512

Other (OTH)

AF:

0.00

AC:

AN:

740

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.330

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

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

Publications

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2-158826494-CATATATATATAT-CATATATATATATATATATATATATAT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over