Genetic Variant NM_001017920.3:c.135C>T (chr2-158804358-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001017920.3(DAPL1):c.135C>T(p.Phe45Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,606,386 control chromosomes in the GnomAD database, including 12,675 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.097 ( 942 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11733 hom. )

Consequence

DAPL1
NM_001017920.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0260

Publications

10 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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP7

Synonymous conserved (PhyloP=-0.026 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAPL1	NM_001017920.3 link	c.135C>T	p.Phe45Phe	synonymous_variant	Exon 2 of 4	ENST00000309950.8	NP_001017920.2	A0PJW8M1E9T5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DAPL1	ENST00000309950.8 link	c.135C>T	p.Phe45Phe	synonymous_variant	Exon 2 of 4	1	NM_001017920.3	ENSP00000309538.4	A0PJW8
DAPL1	ENST00000621326.4 link	c.135C>T	p.Phe45Phe	synonymous_variant	Exon 2 of 5	1		ENSP00000479872.1	M1EA23
DAPL1	ENST00000343761.4 link	c.60C>T	p.Phe20Phe	synonymous_variant	Exon 1 of 4	3		ENSP00000385306.2	H0Y3U5
DAPL1	ENST00000409042.5 link	c.135C>T	p.Phe45Phe	synonymous_variant	Exon 2 of 5	4		ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes

AF:

0.0975

AC:

14813

AN:

152004

Hom.:

942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0343

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0374

Gnomad FIN

AF:

0.175

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.128

GnomAD2 exomes

AF:

0.100

AC:

24446

AN:

243370

AF XY:

0.102

show subpopulations

Gnomad AFR exome

AF:

0.0299

Gnomad AMR exome

AF:

0.0748

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.000333

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.131

Gnomad OTH exome

AF:

0.121

GnomAD4 exome

AF:

0.120

AC:

174093

AN:

1454264

Hom.:

11733

Cov.:

AF XY:

0.118

AC XY:

85484

AN XY:

723118

show subpopulations

African (AFR)

AF:

0.0296

AC:

984

AN:

33290

American (AMR)

AF:

0.0774

AC:

3417

AN:

44122

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

3388

AN:

25890

East Asian (EAS)

AF:

0.000252

AC:

AN:

39644

South Asian (SAS)

AF:

0.0458

AC:

3909

AN:

85320

European-Finnish (FIN)

AF:

0.174

AC:

9234

AN:

53156

Middle Eastern (MID)

AF:

0.115

AC:

662

AN:

5746

European-Non Finnish (NFE)

AF:

0.132

AC:

145729

AN:

1107032

Other (OTH)

AF:

0.113

AC:

6760

AN:

60064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

6672

13343

20015

26686

33358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5076

10152

15228

20304

25380

<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:

0.0974

AC:

14813

AN:

152122

Hom.:

942

Cov.:

AF XY:

0.0974

AC XY:

7242

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0342

AC:

1420

AN:

41500

American (AMR)

AF:

0.102

AC:

1557

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

478

AN:

3468

East Asian (EAS)

AF:

0.000770

AC:

AN:

5192

South Asian (SAS)

AF:

0.0378

AC:

182

AN:

4814

European-Finnish (FIN)

AF:

0.175

AC:

1853

AN:

10560

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.132

AC:

8989

AN:

67998

Other (OTH)

AF:

0.127

AC:

268

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

682

1363

2045

2726

3408

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.120

Hom.:

1899

Bravo

AF:

0.0903

Asia WGS

AF:

0.0290

AC:

102

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

4.3

(source)

DANN

Benign

0.72

PhyloP100

-0.026

PromoterAI

-0.093

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over