Genetic Variant DAPL1:c.224+8_224+9delAT (chr2-158826494-CAT-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The ENST00000343761.4(DAPL1):c.224+8_224+9delAT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 261,732 control chromosomes in the GnomAD database, including 631 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0092 ( 41 hom., cov: 14)

Exomes 𝑓: 0.030 ( 590 hom. )

Consequence

DAPL1
ENST00000343761.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.730

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: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.03 (6043/201402) while in subpopulation SAS AF = 0.0304 (521/17112). AF 95% confidence interval is 0.0283. There are 590 homozygotes in GnomAdExome4. There are 3215 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 41 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+8_224+9delAT		splice_region intron	N/A	ENSP00000385306.2	H0Y3U5
	DAPL1	ENST00000409042.5	TSL:4	c.299+8_299+9delAT		splice_region intron	N/A	ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes

AF:

0.00911

AC:

549

AN:

60288

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00248

Gnomad AMI

AF:

0.00355

Gnomad AMR

AF:

0.00929

Gnomad ASJ

AF:

0.00683

Gnomad EAS

AF:

0.0103

Gnomad SAS

AF:

0.0189

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0120

Gnomad OTH

AF:

0.0111

GnomAD4 exome

AF:

0.0300

AC:

6043

AN:

201402

Hom.:

590

AF XY:

0.0293

AC XY:

3215

AN XY:

109778

show subpopulations

African (AFR)

AF:

0.00315

AC:

AN:

6030

American (AMR)

AF:

0.0193

AC:

149

AN:

7736

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

116

AN:

5016

East Asian (EAS)

AF:

0.00901

AC:

109

AN:

12104

South Asian (SAS)

AF:

0.0304

AC:

521

AN:

17112

European-Finnish (FIN)

AF:

0.166

AC:

2842

AN:

17150

Middle Eastern (MID)

AF:

0.0110

AC:

AN:

730

European-Non Finnish (NFE)

AF:

0.0170

AC:

2147

AN:

126532

Other (OTH)

AF:

0.0147

AC:

132

AN:

8992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

140

280

421

561

701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.00917

AC:

553

AN:

60330

Hom.:

Cov.:

AF XY:

0.00942

AC XY:

259

AN XY:

27506

show subpopulations

African (AFR)

AF:

0.00253

AC:

AN:

16572

American (AMR)

AF:

0.00962

AC:

AN:

5720

Ashkenazi Jewish (ASJ)

AF:

0.00683

AC:

AN:

1610

East Asian (EAS)

AF:

0.0103

AC:

AN:

3778

South Asian (SAS)

AF:

0.0186

AC:

AN:

1994

European-Finnish (FIN)

AF:

0.0143

AC:

AN:

1046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0120

AC:

343

AN:

28514

Other (OTH)

AF:

0.0135

AC:

AN:

740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

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:

0.0179

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.73

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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2-158826494-CATATATATATAT-CATATATATAT

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