Genetic Variant DPYSL2:c.628+11606T>C (chr8-26595589-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001197293.3(DPYSL2):c.628+11606T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,090 control chromosomes in the GnomAD database, including 27,161 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 0.59 ( 27161 hom., cov: 33)

Consequence

DPYSL2
NM_001197293.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.35

Publications

8 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001197293.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DPYSL2	NM_001197293.3	MANE Select	c.628+11606T>C	intron	N/A	NP_001184222.1	A0A1C7CYX9
DPYSL2	NM_001386.6		c.313+11606T>C	intron	N/A	NP_001377.1	Q16555-1
DPYSL2	NM_001244604.2		c.205+11606T>C	intron	N/A	NP_001231533.1	Q16555-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DPYSL2	ENST00000521913.7	TSL:1 MANE Select	c.628+11606T>C	intron	N/A	ENSP00000427985.2	A0A1C7CYX9
DPYSL2	ENST00000311151.9	TSL:1	c.313+11606T>C	intron	N/A	ENSP00000309539.5	Q16555-1
DPYSL2	ENST00000523027.1	TSL:2	c.205+11606T>C	intron	N/A	ENSP00000431117.1	Q16555-2

Frequencies

GnomAD3 genomes

AF:

0.586

AC:

89045

AN:

151974

Hom.:

27143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.412

Gnomad AMI

AF:

0.775

Gnomad AMR

AF:

0.635

Gnomad ASJ

AF:

0.626

Gnomad EAS

AF:

0.794

Gnomad SAS

AF:

0.579

Gnomad FIN

AF:

0.665

Gnomad MID

AF:

0.586

Gnomad NFE

AF:

0.648

Gnomad OTH

AF:

0.594

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.586

AC:

89105

AN:

152090

Hom.:

27161

Cov.:

AF XY:

0.589

AC XY:

43779

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.412

AC:

17080

AN:

41482

American (AMR)

AF:

0.636

AC:

9712

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.626

AC:

2173

AN:

3470

East Asian (EAS)

AF:

0.793

AC:

4090

AN:

5156

South Asian (SAS)

AF:

0.579

AC:

2793

AN:

4822

European-Finnish (FIN)

AF:

0.665

AC:

7039

AN:

10592

Middle Eastern (MID)

AF:

0.582

AC:

170

AN:

292

European-Non Finnish (NFE)

AF:

0.649

AC:

44087

AN:

67974

Other (OTH)

AF:

0.593

AC:

1254

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1791

3583

5374

7166

8957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<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:

0.613

Hom.:

35255

Bravo

AF:

0.580

Asia WGS

AF:

0.636

AC:

2208

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.53

(source)

DANN

Benign

0.35

PhyloP100

-1.3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over