Genetic Variant DAPL1:c.224+7_224+8insATATATATATATATATATATATATAT (chr2-158826494-C-CATATATATATATATATATATATATAT) – 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+8insATATATATATATATATATATATATAT 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 0.0039 ( 27 hom., cov: 14)

Exomes 𝑓: 0.00076 ( 42 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 42 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+8insATATATATATATATATATATATATAT		splice_region intron	N/A	ENSP00000385306.2	H0Y3U5
	DAPL1	ENST00000409042.5	TSL:4	c.299+7_299+8insATATATATATATATATATATATATAT		splice_region intron	N/A	ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes

AF:

0.00390

AC:

235

AN:

60188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00539

Gnomad AMI

AF:

0.00709

Gnomad AMR

AF:

0.00123

Gnomad ASJ

AF:

0.00436

Gnomad EAS

AF:

0.000264

Gnomad SAS

AF:

0.00498

Gnomad FIN

AF:

0.00191

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00408

Gnomad OTH

AF:

0.00139

GnomAD4 exome

AF:

0.000758

AC:

153

AN:

201796

Hom.:

Cov.:

AF XY:

0.000764

AC XY:

AN XY:

110008

show subpopulations

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

African (AFR)

AF:

0.000166

AC:

AN:

6034

American (AMR)

AF:

0.000258

AC:

AN:

7742

Ashkenazi Jewish (ASJ)

AF:

0.00

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:

0.00662

AC:

114

AN:

17210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

730

European-Non Finnish (NFE)

AF:

0.000284

AC:

AN:

126792

Other (OTH)

AF:

0.00

AC:

AN:

9008

⚠️ 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: 0.336

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:

0.00390

AC:

235

AN:

60230

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

AN XY:

27466

show subpopulations

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

African (AFR)

AF:

0.00538

AC:

AN:

16546

American (AMR)

AF:

0.00123

AC:

AN:

5714

Ashkenazi Jewish (ASJ)

AF:

0.00436

AC:

AN:

1604

East Asian (EAS)

AF:

0.000265

AC:

AN:

3778

South Asian (SAS)

AF:

0.00501

AC:

AN:

1996

European-Finnish (FIN)

AF:

0.00191

AC:

AN:

1048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00408

AC:

116

AN:

28448

Other (OTH)

AF:

0.00135

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: 0.314

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

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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2-158826494-CATATATATATAT-CATATATATATATATATATATATATATATATATATATAT

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