rs16843372

Variant names:

• chr2-158813937-T-C
• rs16843372
• NM_001017920.3:c.208-1768T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017920.3(DAPL1):​c.208-1768T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,992 control chromosomes in the GnomAD database, including 23,788 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23788 hom., cov: 31)
• Consequence: DAPL1 NM_001017920.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

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.208-1768T>C		intron	N/A	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.208-1768T>C		intron	N/A	ENSP00000309538.4	A0PJW8
	DAPL1	ENST00000621326.4	TSL:1	c.327-1768T>C		intron	N/A	ENSP00000479872.1	M1EA23
	DAPL1	ENST00000343761.4	TSL:3	c.132+6822T>C		intron	N/A	ENSP00000385306.2	H0Y3U5

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83367 AN: 151874 Hom.: 23760 Cov.: 31

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.0996

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.580

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.549 AC: 83433 AN: 151992 Hom.: 23788 Cov.: 31 AF XY: 0.544 AC XY: 40413 AN XY: 74284

African (AFR) AF: 0.571 AC: 23656 AN: 41456

American (AMR) AF: 0.465 AC: 7095 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1915 AN: 3470

East Asian (EAS) AF: 0.0994 AC: 515 AN: 5180

South Asian (SAS) AF: 0.354 AC: 1706 AN: 4816

European-Finnish (FIN) AF: 0.654 AC: 6918 AN: 10570

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39690 AN: 67920

Other (OTH) AF: 0.576 AC: 1217 AN: 2112

Alfa AF: 0.562 Hom.: 67663

Bravo AF: 0.535

Asia WGS AF: 0.266 AC: 928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.2
DANN	Benign	0.80
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16843372; hg19: chr2-159670449;