8-26643976-C-G

Position:

chr8-26643976-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2

The NM_001197293.3(DPYSL2):c.1310C>G(p.Ala437Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000929 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

DPYSL2
NM_001197293.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DPYSL2. . Gene score misZ 3.8756 (greater than the threshold 3.09). Trascript score misZ 3.9251 (greater than threshold 3.09). GenCC has associacion of gene with schizophrenia.

BP4

Computational evidence support a benign effect (MetaRNN=0.30983666).

BS2

High AC in GnomAdExome4 at 148 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DPYSL2	NM_001197293.3 linkuse as main transcript	c.1310C>G	p.Ala437Gly	missense_variant	10/14	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6 linkuse as main transcript	c.995C>G	p.Ala332Gly	missense_variant	10/14		NP_001377.1
DPYSL2	NM_001244604.2 linkuse as main transcript	c.887C>G	p.Ala296Gly	missense_variant	10/14		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7 linkuse as main transcript	c.1310C>G	p.Ala437Gly	missense_variant	10/14	1	NM_001197293.3	ENSP00000427985
DPYSL2	ENST00000311151.9 linkuse as main transcript	c.995C>G	p.Ala332Gly	missense_variant	10/14	1		ENSP00000309539	P1	Q16555-1
DPYSL2	ENST00000523027.1 linkuse as main transcript	c.887C>G	p.Ala296Gly	missense_variant	10/14	2		ENSP00000431117		Q16555-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251024

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000101

AC:

148

AN:

1461776

Hom.:

Cov.:

AF XY:

0.0000921

AC XY:

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.1310C>G (p.A437G) alteration is located in exon 10 (coding exon 10) of the DPYSL2 gene. This alteration results from a C to G substitution at nucleotide position 1310, causing the alanine (A) at amino acid position 437 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

.;T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

0.019

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.044

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-0.42

MutationAssessor

Benign

0.86

.;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.0

.;N;N

REVEL

Uncertain

0.35

Sift

Benign

0.26

.;T;T

Sift4G

Benign

0.18

.;T;T

Polyphen

0.0

.;B;.

Vest4

0.42, 0.42

MVP

0.43

MPC

0.86

ClinPred

0.11

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.48

gMVP

0.94

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over