Genetic Variant DPYSL2:c.*1916C>T (chr8-26657622-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001197293.3(DPYSL2):c.*1916C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 152,460 control chromosomes in the GnomAD database, including 624 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.088 ( 618 hom., cov: 33)

Exomes 𝑓: 0.14 ( 6 hom. )

Consequence

DPYSL2
NM_001197293.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.73

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

DPYSL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DPYSL2	NM_001197293.3 link	c.*1916C>T	3_prime_UTR_variant	Exon 14 of 14	ENST00000521913.7	NP_001184222.1	Q16555Q59GB4A0A1C7CYX9
DPYSL2	NM_001386.6 link	c.*1916C>T	3_prime_UTR_variant	Exon 14 of 14		NP_001377.1	Q16555-1
DPYSL2	NM_001244604.2 link	c.*1916C>T	3_prime_UTR_variant	Exon 14 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.*1916C>T		3_prime_UTR_variant	Exon 14 of 14	1	NM_001197293.3	ENSP00000427985.2		A0A1C7CYX9
DPYSL2	ENST00000311151.9 link	c.*1916C>T		3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000309539.5		Q16555-1

Frequencies

GnomAD3 genomes

AF:

0.0883

AC:

13409

AN:

151912

Hom.:

618

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0727

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0562

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.134

Gnomad SAS

AF:

0.0758

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0972

Gnomad OTH

AF:

0.0742

GnomAD4 exome

AF:

0.137

AC:

AN:

430

Hom.:

Cov.:

AF XY:

0.150

AC XY:

AN XY:

260

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.134

AC:

AN:

424

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0882

AC:

13411

AN:

152030

Hom.:

618

Cov.:

AF XY:

0.0888

AC XY:

6596

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0726

AC:

3010

AN:

41480

American (AMR)

AF:

0.0560

AC:

856

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

378

AN:

3470

East Asian (EAS)

AF:

0.134

AC:

692

AN:

5176

South Asian (SAS)

AF:

0.0759

AC:

366

AN:

4824

European-Finnish (FIN)

AF:

0.125

AC:

1314

AN:

10514

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0972

AC:

6605

AN:

67966

Other (OTH)

AF:

0.0739

AC:

156

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

617

1234

1852

2469

3086

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.0908

Hom.:

211

Bravo

AF:

0.0830

Asia WGS

AF:

0.0930

AC:

324

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over