Variant 1-85182195-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032184.2(SYDE2):c.2447T>C(p.Val816Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000756 in 1,455,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

SYDE2
NM_032184.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.91

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYDE2	NM_032184.2 linkuse as main transcript	c.2447T>C	p.Val816Ala	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.2447T>C	p.Val816Ala	missense_variant	3/7	5	NM_032184.2	ENSP00000340594.5	Q5VT97-1
SYDE2	ENST00000234668.6 linkuse as main transcript	n.1964T>C		non_coding_transcript_exon_variant	3/3	1
SYDE2	ENST00000696556.1 linkuse as main transcript	c.3038T>C	p.Val1013Ala	missense_variant	3/7			ENSP00000512715.1	A0A8Q3WMH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000838

AC:

AN:

238658

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

129200

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000756

AC:

AN:

1455984

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

723674

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:

0.00000992

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ExAC

AF:

0.0000166

AC:

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

May 24, 2023

The c.2447T>C (p.V816A) 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 2447, causing the valine (V) at amino acid position 816 to be replaced by an alanine (A). 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

Benign

0.20

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.72

M_CAP

Benign

0.020

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-0.76

MutationAssessor

Pathogenic

3.0

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.26

Sift

Benign

0.077

Sift4G

Uncertain

0.0020

Polyphen

0.87

Vest4

0.73

MutPred

0.42

Gain of catalytic residue at Q819 (P = 0.0885);

MVP

0.74

MPC

0.57

ClinPred

0.83

GERP RS

5.8

Varity_R

0.29

gMVP

0.68

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