2-158795385-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001017920.3(DAPL1):​c.13G>C​(p.Val5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,403,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: DAPL1 NM_001017920.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11091095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAPL1	NM_001017920.3	c.13G>C	p.Val5Leu	missense_variant	Exon 1 of 4	ENST00000309950.8	NP_001017920.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAPL1	ENST00000309950.8	c.13G>C	p.Val5Leu	missense_variant	Exon 1 of 4	1	NM_001017920.3	ENSP00000309538.4
DAPL1	ENST00000621326.4	c.13G>C	p.Val5Leu	missense_variant	Exon 1 of 5	1		ENSP00000479872.1
DAPL1	ENST00000409042.5	c.13G>C	p.Val5Leu	missense_variant	Exon 1 of 5	4		ENSP00000386422.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1403466 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 692564

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: 9.25e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T;.;T
Eigen	Benign	0.015
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.5	L;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.69	N;.;N
REVEL	Benign	0.11
Sift	Benign	0.24	T;.;T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.23	B;.;.
Vest4		0.19
MutPred		0.13		Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP		0.13
MPC		0.034
ClinPred		0.52	D
GERP RS		6.0
Varity_R		0.081
gMVP		0.082

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-159651897;