chr2-158807087-T-A

Variant names:

• chr2-158807087-T-A
• rs9869
• NM_001017920.3:c.179T>A

Variant summary

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

The NM_001017920.3(DAPL1):​c.179T>A​(p.Leu60Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DAPL1 NM_001017920.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.14
• Publications: 35 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 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.179T>A	p.Leu60Gln	missense_variant	Exon 3 of 4	ENST00000309950.8	NP_001017920.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAPL1	ENST00000309950.8	c.179T>A	p.Leu60Gln	missense_variant	Exon 3 of 4	1	NM_001017920.3	ENSP00000309538.4
DAPL1	ENST00000621326.4	c.179T>A	p.Leu60Gln	missense_variant	Exon 3 of 5	1		ENSP00000479872.1
DAPL1	ENST00000343761.4	c.104T>A	p.Leu35Gln	missense_variant	Exon 2 of 4	3		ENSP00000385306.2
DAPL1	ENST00000409042.5	c.179T>A	p.Leu60Gln	missense_variant	Exon 3 of 5	4		ENSP00000386422.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459230 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 725966

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 85852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110296

Other (OTH) AF: 0.00 AC: 0 AN: 60244

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T;.;T
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.0	M;.;.
PhyloP100		4.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.82	N;.;D
REVEL	Benign	0.055
Sift	Benign	0.16	T;.;D
Sift4G	Benign	0.17	T;D;D
Polyphen		0.34	B;.;.
Vest4		0.43
MutPred		0.42		Loss of stability (P = 0.0327);Loss of stability (P = 0.0327);Loss of stability (P = 0.0327);
MVP		0.21
MPC		0.036
ClinPred		0.86	D
GERP RS		5.6
Varity_R		0.35
gMVP		0.16
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs9869; hg19: chr2-159663599;