Genetic Variant DPYSL5:p.Arg9Arg (chr2-26898526-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_020134.4(DPYSL5):c.27G>A(p.Arg9Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00935 in 1,614,118 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0097 ( 92 hom. )

Consequence

DPYSL5
NM_020134.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.751

Variant links:

Genes affected

DPYSL5 (HGNC:20637): (dihydropyrimidinase like 5) This gene encodes a member of the CRMP (collapsing response mediator protein) family thought to be involved in neural development. Antibodies to the encoded protein were found in some patients with neurologic symptoms who had paraneoplastic syndrome. A pseudogene of this gene is found on chromosome 11. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Dec 2011]

DPYSL5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 2-26898526-G-A is Benign according to our data. Variant chr2-26898526-G-A is described in ClinVar as [Benign]. Clinvar id is 2650752.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.751 with no splicing effect.

BS2

High AC in GnomAd4 at 945 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPYSL5	NM_020134.4 link	c.27G>A	p.Arg9Arg	synonymous_variant	Exon 2 of 13	ENST00000288699.11	NP_064519.2	Q9BPU6
DPYSL5	NM_001253723.2 link	c.27G>A	p.Arg9Arg	synonymous_variant	Exon 2 of 13		NP_001240652.1	Q9BPU6
DPYSL5	NM_001253724.2 link	c.27G>A	p.Arg9Arg	synonymous_variant	Exon 2 of 13		NP_001240653.1	Q9BPU6
DPYSL5	XM_024453007.2 link	c.27G>A	p.Arg9Arg	synonymous_variant	Exon 2 of 13		XP_024308775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPYSL5	ENST00000288699.11 link	c.27G>A	p.Arg9Arg	synonymous_variant	Exon 2 of 13	1	NM_020134.4	ENSP00000288699.6		Q9BPU6

Frequencies

GnomAD3 genomes

AF:

0.00620

AC:

944

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0182

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00929

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00685

AC:

1721

AN:

251234

AF XY:

0.00700

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0162

Gnomad NFE exome

AF:

0.0104

Gnomad OTH exome

AF:

0.00734

GnomAD4 exome

AF:

0.00968

AC:

14151

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00948

AC XY:

6897

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.00152

AC:

AN:

44718

Gnomad4 ASJ exome

AF:

0.000421

AC:

AN:

26128

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.00201

AC:

173

AN:

86258

Gnomad4 FIN exome

AF:

0.0160

AC:

856

AN:

53420

Gnomad4 NFE exome

AF:

0.0112

AC:

12482

AN:

1111988

Gnomad4 Remaining exome

AF:

0.00803

AC:

485

AN:

60396

Heterozygous variant carriers

860

1720

2579

3439

4299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

492

984

1476

1968

2460

<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:

0.00621

AC:

945

AN:

152262

Hom.:

Cov.:

AF XY:

0.00663

AC XY:

494

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00154

AC:

0.00154031

AN:

0.00154031

Gnomad4 AMR

AF:

0.00255

AC:

0.00254935

AN:

0.00254935

Gnomad4 ASJ

AF:

0.000576

AC:

0.000576369

AN:

0.000576369

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00145

AC:

0.00145228

AN:

0.00145228

Gnomad4 FIN

AF:

0.0182

AC:

0.0182007

AN:

0.0182007

Gnomad4 NFE

AF:

0.00931

AC:

0.00930745

AN:

0.00930745

Gnomad4 OTH

AF:

0.00237

AC:

0.00236518

AN:

0.00236518

Heterozygous variant carriers

101

151

202

252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00729

Hom.:

Bravo

AF:

0.00510

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00905

EpiControl

AF:

0.00853

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DPYSL5: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

8.0

DANN

Benign

0.71

Mutation Taster

=100/0

polymorphism

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