8-26577992-CT-CTTT

Variant names:

• chr8-26577992-C-CTT
• rs3837184
• ENST00000311151.9:c.-262_-261dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000311151.9(DPYSL2):​c.-262_-261dupTT 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
• Publications: 1 publications found

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]

DPYSL2 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3	c.355-3976_355-3975dupTT		intron_variant	Intron 1 of 13	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6	c.-262_-261dupTT		5_prime_UTR_variant	Exon 1 of 14		NP_001377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000311151.9	c.-262_-261dupTT		5_prime_UTR_variant	Exon 1 of 14	1		ENSP00000309539.5
DPYSL2	ENST00000521913.7	c.355-3976_355-3975dupTT		intron_variant	Intron 1 of 13	1	NM_001197293.3	ENSP00000427985.2
DPYSL2	ENST00000493789.6	c.255+626_255+627dupTT		intron_variant	Intron 1 of 2	4		ENSP00000427954.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.041

Splicing

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

Other links and lift over

dbSNP: rs3837184; hg19: chr8-26435508;