Variant chr1-85182547-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032184.2(SYDE2):c.2095T>C(p.Ser699Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,613,904 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: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

SYDE2
NM_032184.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.81

Variant links:

Genes affected

SYDE2 (HGNC:25841): (synapse defective Rho GTPase homolog 2) Predicted to enable GTPase activator activity. Acts upstream of or within cell migration. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

SYDE2 links:

SYDE2 (HGNC:):

SYDE2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37016684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYDE2	NM_032184.2 linkuse as main transcript	c.2095T>C	p.Ser699Pro	missense_variant	3/7	ENST00000341460.6	NP_115560.1	Q5VT97-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SYDE2	ENST00000341460.6 linkuse as main transcript	c.2095T>C	p.Ser699Pro	missense_variant	3/7	5	NM_032184.2	ENSP00000340594.5	Q5VT97-1
SYDE2	ENST00000234668.6 linkuse as main transcript	n.1612T>C		non_coding_transcript_exon_variant	3/3	1
SYDE2	ENST00000696556.1 linkuse as main transcript	c.2686T>C	p.Ser896Pro	missense_variant	3/7			ENSP00000512715.1	A0A8Q3WMH8

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000846

AC:

AN:

248176

Hom.:

AF XY:

0.0000446

AC XY:

AN XY:

134598

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000169

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000137

AC:

200

AN:

1461612

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

727068

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:

0.000175

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000112

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000244

AC:

ExAC

AF:

0.0000828

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.2095T>C (p.S699P) alteration is located in exon 3 (coding exon 3) of the SYDE2 gene. This alteration results from a T to C substitution at nucleotide position 2095, causing the serine (S) at amino acid position 699 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

Eigen

Benign

-0.092

Eigen_PC

Benign

0.0022

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.68

M_CAP

Benign

0.024

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.0

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.36

Sift

Benign

0.16

Sift4G

Benign

0.14

Polyphen

0.23

Vest4

0.86

MVP

0.23

MPC

0.61

ClinPred

0.15

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.36

gMVP

0.72

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