Variant 8-26581971-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001197293.3(DPYSL2):c.357C>T(p.Ser119=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,613,358 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 2 hom. )

Consequence

DPYSL2
NM_001197293.3 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.457

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 8-26581971-C-T is Benign according to our data. Variant chr8-26581971-C-T is described in ClinVar as [Benign]. Clinvar id is 777831.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.457 with no splicing effect.

BS2

High AC in GnomAd4 at 158 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DPYSL2	NM_001197293.3 linkuse as main transcript	c.357C>T	p.Ser119=	splice_region_variant, synonymous_variant	2/14	ENST00000521913.7	NP_001184222.1
DPYSL2	NM_001386.6 linkuse as main transcript	c.42C>T	p.Ser14=	splice_region_variant, synonymous_variant	2/14		NP_001377.1
DPYSL2	NM_001244604.2 linkuse as main transcript	c.-67C>T		splice_region_variant, 5_prime_UTR_variant	2/14		NP_001231533.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYSL2	ENST00000521913.7 linkuse as main transcript	c.357C>T	p.Ser119=	splice_region_variant, synonymous_variant	2/14	1	NM_001197293.3	ENSP00000427985
DPYSL2	ENST00000311151.9 linkuse as main transcript	c.42C>T	p.Ser14=	splice_region_variant, synonymous_variant	2/14	1		ENSP00000309539	P1	Q16555-1
DPYSL2	ENST00000493789.6 linkuse as main transcript	c.258C>T	p.Ser86=	splice_region_variant, synonymous_variant	2/3	4		ENSP00000427954
DPYSL2	ENST00000523027.1 linkuse as main transcript	c.-67C>T		splice_region_variant, 5_prime_UTR_variant	2/14	2		ENSP00000431117		Q16555-2

Frequencies

GnomAD3 genomes

AF:

0.00104

AC:

158

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00110

AC:

276

AN:

251184

Hom.:

AF XY:

0.00110

AC XY:

150

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000279

Gnomad NFE exome

AF:

0.00220

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00171

AC:

2498

AN:

1461068

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

1210

AN XY:

726882

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000263

Gnomad4 NFE exome

AF:

0.00216

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.00104

AC:

158

AN:

152290

Hom.:

Cov.:

AF XY:

0.000900

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00193

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.00104

EpiCase

AF:

0.00213

EpiControl

AF:

0.00160

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

Labcorp Genetics (formerly Invitae), Labcorp

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

6.0

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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