Genetic Variant DAPL1:c.224+7_224+8insATATATATATATATATATATATAT (chr2-158826494-C-CATATATATATATATATATATATAT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000343761.4(DAPL1):c.224+7_224+8insATATATATATATATATATATATAT 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 0.0040 ( 26 hom., cov: 14)

Exomes 𝑓: 0.0012 ( 70 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 70 AR gene

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

Frequencies

GnomAD3 genomes

AF:

0.00395

AC:

238

AN:

60182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00388

Gnomad AMI

AF:

0.00709

Gnomad AMR

AF:

0.00298

Gnomad ASJ

AF:

0.00436

Gnomad EAS

AF:

0.00132

Gnomad SAS

AF:

0.00349

Gnomad FIN

AF:

0.000956

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00467

Gnomad OTH

AF:

0.00278

GnomAD4 exome

AF:

0.00124

AC:

250

AN:

201766

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

119

AN XY:

109988

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:

0.00

AC:

AN:

7742

Ashkenazi Jewish (ASJ)

AF:

0.000398

AC:

AN:

5024

East Asian (EAS)

AF:

0.00

AC:

AN:

12116

South Asian (SAS)

AF:

0.00

AC:

AN:

17140

European-Finnish (FIN)

AF:

0.0107

AC:

183

AN:

17176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

730

European-Non Finnish (NFE)

AF:

0.000513

AC:

AN:

126794

Other (OTH)

AF:

0.00

AC:

AN:

9010

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.356

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00395

AC:

238

AN:

60224

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

112

AN XY:

27470

show subpopulations

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

African (AFR)

AF:

0.00387

AC:

AN:

16532

American (AMR)

AF:

0.00298

AC:

AN:

5712

Ashkenazi Jewish (ASJ)

AF:

0.00436

AC:

AN:

1606

East Asian (EAS)

AF:

0.00132

AC:

AN:

3774

South Asian (SAS)

AF:

0.00352

AC:

AN:

1990

European-Finnish (FIN)

AF:

0.000956

AC:

AN:

1046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00467

AC:

133

AN:

28468

Other (OTH)

AF:

0.00270

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: 0.348

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00125

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.092

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over