2-158795385-G-T

Variant names:

• chr2-158795385-G-T
• rs138581432
• NM_001017920.3:c.13G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001017920.3(DAPL1):​c.13G>T​(p.Val5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V5M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DAPL1 NM_001017920.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10976073).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017920.3. 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
	DAPL1	NM_001017920.3	MANE Select	c.13G>T	p.Val5Leu	missense	Exon 1 of 4	NP_001017920.2	M1E9T5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAPL1	ENST00000309950.8	TSL:1 MANE Select	c.13G>T	p.Val5Leu	missense	Exon 1 of 4	ENSP00000309538.4	A0PJW8
	DAPL1	ENST00000621326.4	TSL:1	c.13G>T	p.Val5Leu	missense	Exon 1 of 5	ENSP00000479872.1	M1EA23
	DAPL1	ENST00000409042.5	TSL:4	c.13G>T	p.Val5Leu	missense	Exon 1 of 5	ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	0.015
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.2
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.11
Sift	Benign	0.24	T
Sift4G	Benign	0.22	T
Polyphen		0.23	B
Vest4		0.19
MutPred		0.13		Gain of helix (P = 0.062)
MVP		0.13
MPC		0.034
ClinPred		0.52	D
GERP RS		6.0
PromoterAI		-0.033	Neutral
Varity_R		0.081
gMVP		0.082
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs138581432; hg19: chr2-159651897;