8-26595589-T-A

Variant names:

• chr8-26595589-T-A
• rs5029306
• NM_001197293.3:c.628+11606T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001197293.3(DPYSL2):​c.628+11606T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001197293.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL2	NM_001197293.3	MANE Select	c.628+11606T>A		intron	N/A	NP_001184222.1
	DPYSL2	NM_001386.6		c.313+11606T>A		intron	N/A	NP_001377.1
	DPYSL2	NM_001244604.2		c.205+11606T>A		intron	N/A	NP_001231533.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL2	ENST00000521913.7	TSL:1 MANE Select	c.628+11606T>A		intron	N/A	ENSP00000427985.2
	DPYSL2	ENST00000311151.9	TSL:1	c.313+11606T>A		intron	N/A	ENSP00000309539.5
	DPYSL2	ENST00000523027.1	TSL:2	c.205+11606T>A		intron	N/A	ENSP00000431117.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.41
DANN	Benign	0.70
PhyloP100		-1.3

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

Other links and lift over

dbSNP: rs5029306; hg19: chr8-26453105;