2-158813928-T-G

Position:

• chr2-158813928-T-G

Variant summary

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

The NM_001017920.3(DAPL1):​c.208-1777T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,192 control chromosomes in the GnomAD database, including 1,421 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 0.12 (1421 hom., cov: 32)
• Consequence: DAPL1 NM_001017920.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.745

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAPL1	NM_001017920.3	c.208-1777T>G		intron_variant		ENST00000309950.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAPL1	ENST00000309950.8	c.208-1777T>G		intron_variant		1	NM_001017920.3	P1
DAPL1	ENST00000621326.4	c.327-1777T>G		intron_variant		1
DAPL1	ENST00000343761.4	c.133+6813T>G		intron_variant		3
DAPL1	ENST00000409042.5	c.207+6813T>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18365 AN: 152074 Hom.: 1421 Cov.: 32

Gnomad AFR AF: 0.0352

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0694

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.121 AC: 18357 AN: 152192 Hom.: 1421 Cov.: 32 AF XY: 0.121 AC XY: 8970 AN XY: 74432

Gnomad4 AFR AF: 0.0350

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0701

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.162

Alfa AF: 0.0715 Hom.: 97

Bravo AF: 0.113

Asia WGS AF: 0.0420 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.5
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: rs74923781; hg19: chr2-159670440;