2-158804358-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001017920.3(DAPL1):c.135C>T(p.Phe45=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DAPL1	NM_001017920.3	c.135C>T	p.Phe45=	synonymous_variant	2/4	ENST00000309950.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAPL1	ENST00000309950.8	c.135C>T	p.Phe45=	synonymous_variant	2/4	1	NM_001017920.3	P1
DAPL1	ENST00000621326.4	c.135C>T	p.Phe45=	synonymous_variant	2/5	1
DAPL1	ENST00000343761.4	c.63C>T	p.Phe21=	synonymous_variant	1/4	3
DAPL1	ENST00000409042.5	c.135C>T	p.Phe45=	synonymous_variant	2/5	4

Frequencies

GnomAD3 genomes AF: 0.0975 AC: 14813 AN: 152004 Hom.: 942 Cov.: 32

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

GnomAD3 exomes AF: 0.100 AC: 24446 AN: 243370 Hom.: 1546 AF XY: 0.102 AC XY: 13381 AN XY: 131350

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 SAS exome AF: 0.0458

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.: 30 AF XY: 0.118 AC XY: 85484 AN XY: 723118

Gnomad4 AFR exome AF: 0.0296

Gnomad4 AMR exome AF: 0.0774

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.0458

Gnomad4 FIN exome AF: 0.174

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.0974 AC: 14813 AN: 152122 Hom.: 942 Cov.: 32 AF XY: 0.0974 AC XY: 7242 AN XY: 74356

Gnomad4 AFR AF: 0.0342

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.0378

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.127

Alfa AF: 0.123 Hom.: 1589

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
Dann	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs17810398; hg19: chr2-159660870;