8-26577992-CT-CTT

Position:

• chr8-26577992-CT-CTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000311151.9(DPYSL2):​c.-261dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 26)
• Consequence: DPYSL2 ENST00000311151.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.355-3975dup		intron_variant		ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.-261dup		5_prime_UTR_variant	1/14		NP_001377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000311151.9	c.-261dup		5_prime_UTR_variant	1/14	1		ENSP00000309539	P1
DPYSL2	ENST00000521913.7	c.355-3975dup		intron_variant		1	NM_001197293.3	ENSP00000427985
DPYSL2	ENST00000493789.6	c.255+627dup		intron_variant		4		ENSP00000427954

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3837184; hg19: chr8-26435508;