Genetic Variant DPYSL2:p.Ala259Glu (chr8-26624290-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001197293.3(DPYSL2):c.776C>A(p.Ala259Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A259V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

DPYSL2
NM_001197293.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

Publications

0 publications found

Variant links:

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)

DPYSL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24088752).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPYSL2	NM_001197293.3	MANE Select	c.776C>A	p.Ala259Glu	missense	Exon 4 of 14	NP_001184222.1	A0A1C7CYX9
DPYSL2	NM_001386.6		c.461C>A	p.Ala154Glu	missense	Exon 4 of 14	NP_001377.1	Q16555-1
DPYSL2	NM_001244604.2		c.353C>A	p.Ala118Glu	missense	Exon 4 of 14	NP_001231533.1	Q16555-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPYSL2	ENST00000521913.7	TSL:1 MANE Select	c.776C>A	p.Ala259Glu	missense	Exon 4 of 14	ENSP00000427985.2	A0A1C7CYX9
DPYSL2	ENST00000311151.9	TSL:1	c.461C>A	p.Ala154Glu	missense	Exon 4 of 14	ENSP00000309539.5	Q16555-1
DPYSL2	ENST00000523027.1	TSL:2	c.353C>A	p.Ala118Glu	missense	Exon 4 of 14	ENSP00000431117.1	Q16555-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.083

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.37

Eigen

Benign

-0.067

Eigen_PC

Benign

0.064

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.060

MetaRNN

Benign

0.24

MetaSVM

Uncertain

-0.092

MutationAssessor

Benign

0.96

PhyloP100

4.1

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.39

Sift

Benign

0.46

Sift4G

Benign

0.69

Polyphen

0.76

Vest4

0.44

MutPred

0.55

Gain of disorder (P = 0.0123)

MVP

0.58

MPC

1.0

ClinPred

0.51

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.25

gMVP

0.88

Mutation Taster

=68/32

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over