Genetic Variant DAPL1:c.224+7_224+8insATATATATATATATATATAT (chr2-158826494-C-CATATATATATATATATATAT) – 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+8insATATATATATATATATATAT 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 0.026 ( 325 hom., cov: 14)

Exomes 𝑓: 0.0076 ( 369 hom. )

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 GnomAd4 at 325 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+8insATATATATATATATATATAT		splice_region intron	N/A	ENSP00000385306.2	H0Y3U5
	DAPL1	ENST00000409042.5	TSL:4	c.299+7_299+8insATATATATATATATATATAT		splice_region intron	N/A	ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes

AF:

0.0260

AC:

1564

AN:

60076

Hom.:

325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00642

Gnomad AMI

AF:

0.131

Gnomad AMR

AF:

0.00985

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.00106

Gnomad SAS

AF:

0.00747

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0453

Gnomad OTH

AF:

0.0195

GnomAD4 exome

AF:

0.00765

AC:

1540

AN:

201360

Hom.:

369

Cov.:

AF XY:

0.00746

AC XY:

819

AN XY:

109790

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

6034

American (AMR)

AF:

0.000387

AC:

AN:

7742

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5022

East Asian (EAS)

AF:

0.00

AC:

AN:

12116

South Asian (SAS)

AF:

0.000175

AC:

AN:

17140

European-Finnish (FIN)

AF:

0.0733

AC:

1230

AN:

16780

Middle Eastern (MID)

AF:

0.00137

AC:

AN:

730

European-Non Finnish (NFE)

AF:

0.00225

AC:

285

AN:

126788

Other (OTH)

AF:

0.00200

AC:

AN:

9008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.416

Heterozygous variant carriers

116

145

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:

0.0260

AC:

1564

AN:

60118

Hom.:

325

Cov.:

AF XY:

0.0224

AC XY:

614

AN XY:

27414

show subpopulations

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

African (AFR)

AF:

0.00641

AC:

106

AN:

16536

American (AMR)

AF:

0.00982

AC:

AN:

5704

Ashkenazi Jewish (ASJ)

AF:

0.0219

AC:

AN:

1596

East Asian (EAS)

AF:

0.00106

AC:

AN:

3776

South Asian (SAS)

AF:

0.00752

AC:

AN:

1994

European-Finnish (FIN)

AF:

0.0115

AC:

AN:

1048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0453

AC:

1285

AN:

28370

Other (OTH)

AF:

0.0190

AC:

AN:

738

⚠️ 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: 0.383

Heterozygous variant carriers

140

187

234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00295

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over