rs367948

Positions:

• chr8-26577600-G-C
• chr8-26577600-G-T

Variant summary

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

The NM_001197293.3(DPYSL2):​c.355-4369G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 148,458 control chromosomes in the GnomAD database, including 42,843 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 0.76 (42843 hom., cov: 29)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.84).
• 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.355-4369G>C		intron_variant		ENST00000521913.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPYSL2	ENST00000521913.7	c.355-4369G>C		intron_variant		1	NM_001197293.3
DPYSL2	ENST00000493789.6	c.255+233G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.757 AC: 112249 AN: 148360 Hom.: 42826 Cov.: 29

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.756 AC: 112305 AN: 148458 Hom.: 42843 Cov.: 29 AF XY: 0.758 AC XY: 54890 AN XY: 72450

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.797

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.743

Alfa AF: 0.726 Hom.: 2415

Bravo AF: 0.757

Asia WGS AF: 0.786 AC: 2422 AN: 3082

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs367948; hg19: chr8-26435116;