Genetic Variant DAPL1:c.224+7_224+8insATATATATAT (chr2-158826494-C-CATATATATAT) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The ENST00000343761.4(DAPL1):c.224+7_224+8insATATATATAT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 3 hom., cov: 14)

Exomes 𝑓: 0.0013 ( 64 hom. )

Consequence

DAPL1
ENST00000343761.4 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 2-158826494-C-CATATATATAT is Benign according to our data. Variant chr2-158826494-C-CATATATATAT is described in ClinVar as Likely_benign. ClinVar VariationId is 2651448.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 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+8insATATATATAT		splice_region intron	N/A	ENSP00000385306.2	H0Y3U5
	DAPL1	ENST00000409042.5	TSL:4	c.299+7_299+8insATATATATAT		splice_region intron	N/A	ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes

AF:

0.00149

AC:

AN:

60262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000423

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00498

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.00278

GnomAD4 exome

AF:

0.00133

AC:

268

AN:

201802

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

182

AN XY:

110002

show subpopulations

African (AFR)

AF:

0.000663

AC:

AN:

6034

American (AMR)

AF:

0.00129

AC:

AN:

7738

Ashkenazi Jewish (ASJ)

AF:

0.000996

AC:

AN:

5022

East Asian (EAS)

AF:

0.00

AC:

AN:

12116

South Asian (SAS)

AF:

0.00175

AC:

AN:

17140

European-Finnish (FIN)

AF:

0.00360

AC:

AN:

17220

Middle Eastern (MID)

AF:

0.00137

AC:

AN:

730

European-Non Finnish (NFE)

AF:

0.00115

AC:

146

AN:

126792

Other (OTH)

AF:

0.00111

AC:

AN:

9010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00149

AC:

AN:

60304

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

AN XY:

27500

show subpopulations

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

African (AFR)

AF:

0.000423

AC:

AN:

16564

American (AMR)

AF:

0.00105

AC:

AN:

5718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1608

East Asian (EAS)

AF:

0.00

AC:

AN:

3778

South Asian (SAS)

AF:

0.00502

AC:

AN:

1994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00228

AC:

AN:

28498

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: 0.354

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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

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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2-158826494-CATATATATATAT-CATATATATATATATATATATAT

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