Variant 8-26643977-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001197293.3(DPYSL2):c.1311C>G(p.Ala437=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 1,614,168 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 18 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 105 hom. )

Consequence

DPYSL2
NM_001197293.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.02

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 8-26643977-C-G is Benign according to our data. Variant chr8-26643977-C-G is described in ClinVar as [Benign]. Clinvar id is 777419.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.02 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DPYSL2	NM_001197293.3 linkuse as main transcript	c.1311C>G	p.Ala437=	synonymous_variant	10/14	ENST00000521913.7
DPYSL2	NM_001386.6 linkuse as main transcript	c.996C>G	p.Ala332=	synonymous_variant	10/14
DPYSL2	NM_001244604.2 linkuse as main transcript	c.888C>G	p.Ala296=	synonymous_variant	10/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPYSL2	ENST00000521913.7 linkuse as main transcript	c.1311C>G	p.Ala437=	synonymous_variant	10/14	1	NM_001197293.3
DPYSL2	ENST00000311151.9 linkuse as main transcript	c.996C>G	p.Ala332=	synonymous_variant	10/14	1		P1	Q16555-1
DPYSL2	ENST00000523027.1 linkuse as main transcript	c.888C>G	p.Ala296=	synonymous_variant	10/14	2			Q16555-2

Frequencies

GnomAD3 genomes

AF:

0.00518

AC:

788

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000699

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00656

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00934

AC:

2346

AN:

251086

Hom.:

AF XY:

0.00723

AC XY:

981

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.0603

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0105

Gnomad SAS exome

AF:

0.000556

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00588

GnomAD4 exome

AF:

0.00217

AC:

3179

AN:

1461822

Hom.:

105

Cov.:

AF XY:

0.00188

AC XY:

1365

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.0574

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00970

Gnomad4 SAS exome

AF:

0.000626

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.00516

AC:

786

AN:

152346

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

472

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000697

Gnomad4 AMR

AF:

0.0459

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00638

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.00825

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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