rs1271732197

Variant names:

• chr2-158804288-C-A
• NM_001017920.3:c.65C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-158804288-C-A
• chr2-158804288-C-T

Variant summary

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

The NM_001017920.3(DAPL1):​c.65C>A​(p.Ala22Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,656 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DAPL1 NM_001017920.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAPL1	NM_001017920.3	c.65C>A	p.Ala22Asp	missense_variant	Exon 2 of 4	ENST00000309950.8	NP_001017920.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAPL1	ENST00000309950.8	c.65C>A	p.Ala22Asp	missense_variant	Exon 2 of 4	1	NM_001017920.3	ENSP00000309538.4
DAPL1	ENST00000621326.4	c.65C>A	p.Ala22Asp	missense_variant	Exon 2 of 5	1		ENSP00000479872.1
DAPL1	ENST00000409042.5	c.65C>A	p.Ala22Asp	missense_variant	Exon 2 of 5	4		ENSP00000386422.1
DAPL1	ENST00000343761.4	c.-11C>A		upstream_gene_variant		3		ENSP00000385306.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454656 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 723300

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: 9.03e-7

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	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.;T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Pathogenic	3.5	M;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.9	D;.;D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D;.;D
Sift4G	Uncertain	0.0040	D;T;D
Polyphen		1.0	D;.;.
Vest4		0.76
MutPred		0.61		Gain of relative solvent accessibility (P = 0.0023);Gain of relative solvent accessibility (P = 0.0023);Gain of relative solvent accessibility (P = 0.0023);
MVP		0.48
MPC		0.091
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.96
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-159660800;