DPYSL2 p.Ser247Ser

Variant names:

• chr8-26624252-C-C
• ENST00000521913.7:c.

Your query was ambiguous. Multiple possible variants found:

• chr8-26624253--
• chr8-26624255-T-C
• chr8-26624253-AG-TC
• chr8-26624253-AGT-TCC
• chr8-26624253-AGT-TCA
• chr8-26624253-AGT-TCG

Variant summary

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

The NM_001197293.3(DPYSL2):​c. variant causes a intron change. 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: 32)
• Consequence: DPYSL2 NM_001197293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.10
• Publications: 0 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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL2	NM_001197293.3	MANE Select	c.		intron	N/A	NP_001184222.1	A0A1C7CYX9
	DPYSL2	NM_001386.6		c.		intron	N/A	NP_001377.1	Q16555-1
	DPYSL2	NM_001244604.2		c.		intron	N/A	NP_001231533.1	Q16555-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPYSL2	ENST00000521913.7	TSL:1 MANE Select	c.		exon_region	Exon 4 of 14	ENSP00000427985.2	A0A1C7CYX9
	DPYSL2	ENST00000311151.9	TSL:1	c.		exon_region	Exon 4 of 14	ENSP00000309539.5	Q16555-1
	DPYSL2	ENST00000523027.1	TSL:2	c.		exon_region	Exon 4 of 14	ENSP00000431117.1	Q16555-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-26481768;