chr2-158804358-C-A

Position:

• chr2-158804358-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000309950.8(DAPL1):​c.135C>A​(p.Phe45Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DAPL1 ENST00000309950.8 missense
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.015643775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAPL1	NM_001017920.3	c.135C>A	p.Phe45Leu	missense_variant	2/4	ENST00000309950.8	NP_001017920.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAPL1	ENST00000309950.8	c.135C>A	p.Phe45Leu	missense_variant	2/4	1	NM_001017920.3	ENSP00000309538	P1
DAPL1	ENST00000621326.4	c.135C>A	p.Phe45Leu	missense_variant	2/5	1		ENSP00000479872
DAPL1	ENST00000343761.4	c.63C>A	p.Phe21Leu	missense_variant	1/4	3		ENSP00000385306
DAPL1	ENST00000409042.5	c.135C>A	p.Phe45Leu	missense_variant	2/5	4		ENSP00000386422

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456200 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 724086

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.57
DANN	Benign	0.64
DEOGEN2	Benign	0.0017	T;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.52	T;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.016	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.2	N;.;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.74	N;.;N
REVEL	Benign	0.039
Sift	Benign	0.78	T;.;T
Sift4G	Benign	0.36	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.053
MutPred		0.29		Gain of ubiquitination at K42 (P = 0.07);Gain of ubiquitination at K42 (P = 0.07);Gain of ubiquitination at K42 (P = 0.07);
MVP		0.030
MPC		0.012
ClinPred		0.052	T
GERP RS		-5.9
Varity_R		0.063
gMVP		0.070

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;