rs17810816

Positions:

• chr2-158815480-A-G
• chr2-158815480-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017920.3(DAPL1):​c.208-225A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,220 control chromosomes in the GnomAD database, including 1,468 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 0.13 (1468 hom., cov: 33)
• Consequence: DAPL1 NM_001017920.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAPL1	NM_001017920.3	c.208-225A>G		intron_variant		ENST00000309950.8	NP_001017920.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAPL1	ENST00000309950.8	c.208-225A>G		intron_variant		1	NM_001017920.3	ENSP00000309538.4
DAPL1	ENST00000621326.4	c.327-225A>G		intron_variant		1		ENSP00000479872.1
DAPL1	ENST00000343761.4	c.132+8365A>G		intron_variant		3		ENSP00000385306.2
DAPL1	ENST00000409042.5	c.207+8365A>G		intron_variant		4		ENSP00000386422.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19487 AN: 152102 Hom.: 1468 Cov.: 33

Gnomad AFR AF: 0.0653

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.128 AC: 19477 AN: 152220 Hom.: 1468 Cov.: 33 AF XY: 0.127 AC XY: 9464 AN XY: 74412

Gnomad4 AFR AF: 0.0651

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0670

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.168

Alfa AF: 0.162 Hom.: 4194

Bravo AF: 0.122

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.86
DANN	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs17810816; hg19: chr2-159671992;