Variant 2-26898627-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_020134.4(DPYSL5):c.128T>A(p.Met43Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DPYSL5
NM_020134.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.17

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DPYSL5. . Gene score misZ 3.0829 (greater than the threshold 3.09). Trascript score misZ 3.7328 (greater than threshold 3.09). GenCC has associacion of gene with Ritscher-Schinzel syndrome 4, syndromic intellectual disability.

BP4

Computational evidence support a benign effect (MetaRNN=0.31961328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DPYSL5	NM_020134.4 linkuse as main transcript	c.128T>A	p.Met43Lys	missense_variant	2/13	ENST00000288699.11	NP_064519.2
DPYSL5	NM_001253723.2 linkuse as main transcript	c.128T>A	p.Met43Lys	missense_variant	2/13		NP_001240652.1
DPYSL5	NM_001253724.2 linkuse as main transcript	c.128T>A	p.Met43Lys	missense_variant	2/13		NP_001240653.1
DPYSL5	XM_024453007.2 linkuse as main transcript	c.128T>A	p.Met43Lys	missense_variant	2/13		XP_024308775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPYSL5	ENST00000288699.11 linkuse as main transcript	c.128T>A	p.Met43Lys	missense_variant	2/13	1	NM_020134.4	ENSP00000288699	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Aug 18, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

.;T;T;T;T;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

D;.;.;D;D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.32

T;T;T;T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

-1.6

.;N;N;.;N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.1

D;D;D;D;.;D

REVEL

Uncertain

0.49

Sift

Benign

0.41

T;T;T;T;.;T

Sift4G

Benign

0.94

T;T;T;T;T;T

Polyphen

0.011

.;B;B;.;B;.

Vest4

0.51

MutPred

0.52

Gain of ubiquitination at M43 (P = 0.0219);Gain of ubiquitination at M43 (P = 0.0219);Gain of ubiquitination at M43 (P = 0.0219);Gain of ubiquitination at M43 (P = 0.0219);Gain of ubiquitination at M43 (P = 0.0219);Gain of ubiquitination at M43 (P = 0.0219);

MVP

0.83

MPC

2.3

ClinPred

0.87

GERP RS

4.8

Varity_R

0.86

gMVP

0.90

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over