chr8-26624181-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001197293.3(DPYSL2):c.667G>A(p.Ala223Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,614,186 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 98 hom. )

Consequence

DPYSL2
NM_001197293.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.236

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036204457).

BP6

Variant 8-26624181-G-A is Benign according to our data. Variant chr8-26624181-G-A is described in ClinVar as [Benign]. Clinvar id is 708360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3 link	c.667G>A	p.Ala223Thr	missense_variant	Exon 4 of 14	ENST00000521913.7	NP_001184222.1	Q16555Q59GB4A0A1C7CYX9
DPYSL2	NM_001386.6 link	c.352G>A	p.Ala118Thr	missense_variant	Exon 4 of 14		NP_001377.1	Q16555-1
DPYSL2	NM_001244604.2 link	c.244G>A	p.Ala82Thr	missense_variant	Exon 4 of 14		NP_001231533.1	Q16555-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7 link	c.667G>A	p.Ala223Thr	missense_variant	Exon 4 of 14	1	NM_001197293.3	ENSP00000427985.2		A0A1C7CYX9

Frequencies

GnomAD3 genomes

AF:

0.00283

AC:

430

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0733

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00644

AC:

1620

AN:

251410

AF XY:

0.00605

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0842

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00191

AC:

2791

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00190

AC XY:

1379

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

AC:

AN:

33478

Gnomad4 AMR exome

AF:

0.0000894

AC:

AN:

44724

Gnomad4 ASJ exome

AF:

0.000230

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.0583

AC:

2316

AN:

39700

Gnomad4 SAS exome

AF:

0.00137

AC:

118

AN:

86258

Gnomad4 FIN exome

AF:

0.0000374

AC:

AN:

53420

Gnomad4 NFE exome

AF:

0.000136

AC:

151

AN:

1112010

Gnomad4 Remaining exome

AF:

0.00313

AC:

189

AN:

60394

Heterozygous variant carriers

149

297

446

594

743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00282

AC:

430

AN:

152298

Hom.:

Cov.:

AF XY:

0.00333

AC XY:

248

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000217

AC:

0.000216534

AN:

0.000216534

Gnomad4 AMR

AF:

0.000458

AC:

0.000457516

AN:

0.000457516

Gnomad4 ASJ

AF:

0.000288

AC:

0.000288351

AN:

0.000288351

Gnomad4 EAS

AF:

0.0733

AC:

0.0732792

AN:

0.0732792

Gnomad4 SAS

AF:

0.00311

AC:

0.00311074

AN:

0.00311074

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000221

AC:

0.000220517

AN:

0.000220517

Gnomad4 OTH

AF:

0.00189

AC:

0.00189036

AN:

0.00189036

Heterozygous variant carriers

111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00257

Hom.:

Bravo

AF:

0.00397

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00595

AC:

722

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.32

.;T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.70

T;T;T

MetaRNN

Benign

0.0036

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.83

.;L;.

PrimateAI

Uncertain

0.48

PROVEAN

Benign

0.080

.;N;N

REVEL

Benign

0.14

Sift

Benign

0.19

.;T;T

Sift4G

Benign

0.23

.;T;T

Polyphen

0.078

.;B;.

Vest4

0.078, 0.081

MVP

0.28

MPC

0.82

ClinPred

0.0045

GERP RS

2.6

Varity_R

0.15

gMVP

0.57

Mutation Taster

=93/7

polymorphism (auto)

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