8-26626656-G-A

Position:

chr8-26626656-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2

The NM_001197293.3(DPYSL2):c.833G>A(p.Arg278His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000712 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

DPYSL2
NM_001197293.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.52

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 Benign. Variant got -8 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=0.013752729).

BP6

Variant 8-26626656-G-A is Benign according to our data. Variant chr8-26626656-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3054564.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DPYSL2	NM_001197293.3 linkuse as main transcript	c.833G>A	p.Arg278His	missense_variant	5/14	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6 linkuse as main transcript	c.518G>A	p.Arg173His	missense_variant	5/14		NP_001377.1
DPYSL2	NM_001244604.2 linkuse as main transcript	c.410G>A	p.Arg137His	missense_variant	5/14		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7 linkuse as main transcript	c.833G>A	p.Arg278His	missense_variant	5/14	1	NM_001197293.3	ENSP00000427985
DPYSL2	ENST00000311151.9 linkuse as main transcript	c.518G>A	p.Arg173His	missense_variant	5/14	1		ENSP00000309539	P1	Q16555-1
DPYSL2	ENST00000523027.1 linkuse as main transcript	c.410G>A	p.Arg137His	missense_variant	5/14	2		ENSP00000431117		Q16555-2
DPYSL2	ENST00000523093.5 linkuse as main transcript	n.499G>A		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152178

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:

0.00269

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000294

AC:

AN:

251444

Hom.:

AF XY:

0.000302

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00397

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000677

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00212

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000105

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00270

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000475

Bravo

AF:

0.000155

ExAC

AF:

0.000222

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DPYSL2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 08, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

.;T;.

Eigen

Benign

0.022

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.061

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Uncertain

-0.065

MutationAssessor

Benign

1.4

.;L;.

MutationTaster

Benign

0.94

D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.3

.;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.16

.;T;T

Sift4G

Benign

0.55

.;T;T

Polyphen

0.37

.;B;.

Vest4

0.28, 0.28

MVP

0.73

MPC

1.0

ClinPred

0.076

GERP RS

3.9

Varity_R

0.12

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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