rs400181

chr8-26577607-C-T

Variant summary

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

The NM_001197293.3(DPYSL2):c.355-4362C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 148,826 control chromosomes in the GnomAD database, including 39,187 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 0.71 (39187 hom., cov: 30)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

Genes affected

DPYSL2 (HGNC:3014): (dihydropyrimidinase like 2) This gene encodes a member of the collapsin response mediator protein family. Collapsin response mediator proteins form homo- and hetero-tetramers and facilitate neuron guidance, growth and polarity. The encoded protein promotes microtubule assembly and is required for Sema3A-mediated growth cone collapse, and also plays a role in synaptic signaling through interactions with calcium channels. This gene has been implicated in multiple neurological disorders, and hyperphosphorylation of the encoded protein may play a key role in the development of Alzheimer's disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPYSL2	NM_001197293.3	c.355-4362C>T		intron_variant		ENST00000521913.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPYSL2	ENST00000521913.7	c.355-4362C>T		intron_variant		1	NM_001197293.3
DPYSL2	ENST00000493789.6	c.255+240C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.713 AC: 106019 AN: 148724 Hom.: 39184 Cov.: 30

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.713 AC: 106045 AN: 148826 Hom.: 39187 Cov.: 30 AF XY: 0.716 AC XY: 51965 AN XY: 72626

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.780

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.790

Gnomad4 OTH AF: 0.714

Alfa AF: 0.743 Hom.: 5212

Bravo AF: 0.707

Asia WGS AF: 0.772 AC: 2389 AN: 3094

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	12
Dann	Benign	0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs400181; hg19: chr8-26435123;