rs1271732197

Variant names:

• chr2-158804288-C-T
• rs1271732197
• NM_001017920.3:c.65C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001017920.3(DAPL1):​c.65C>T​(p.Ala22Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,606,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DAPL1 NM_001017920.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.95
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28678912).

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.65C>T	p.Ala22Val	missense	Exon 2 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.65C>T	p.Ala22Val	missense	Exon 2 of 4	ENSP00000309538.4	A0PJW8
	DAPL1	ENST00000621326.4	TSL:1	c.65C>T	p.Ala22Val	missense	Exon 2 of 5	ENSP00000479872.1	M1EA23
	DAPL1	ENST00000409042.5	TSL:4	c.65C>T	p.Ala22Val	missense	Exon 2 of 5	ENSP00000386422.1	B8ZZC6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000412 AC: 1 AN: 242626 AF XY: 0.00000764

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000918

Gnomad OTH exome AF: 0.00

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

African (AFR) AF: 0.00 AC: 0 AN: 33318

American (AMR) AF: 0.00 AC: 0 AN: 44274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25922

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 85010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107474

Other (OTH) AF: 0.00 AC: 0 AN: 60094

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152092 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74278

African (AFR) AF: 0.00 AC: 0 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.65		Gain of MoRF binding (P = 0.1315)
MVP		0.29
MPC		0.077
ClinPred		0.99	D
GERP RS		5.9
PromoterAI		-0.029	Neutral
Varity_R		0.82
gMVP		0.14
Mutation Taster		=92/8	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: rs1271732197; hg19: chr2-159660800;