Variant 1-85169123-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032184.2(SYDE2):c.2774C>T(p.Ser925Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SYDE2
NM_032184.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17085636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYDE2	NM_032184.2 linkuse as main transcript	c.2774C>T	p.Ser925Leu	missense_variant	5/7	ENST00000341460.6	NP_115560.1	Q5VT97-1
SYDE2	XM_017002483.2 linkuse as main transcript	c.2774C>T	p.Ser925Leu	missense_variant	5/7		XP_016857972.2
SYDE2	XM_017002484.3 linkuse as main transcript	c.2774C>T	p.Ser925Leu	missense_variant	5/8		XP_016857973.2
SYDE2	XM_047431920.1 linkuse as main transcript	c.*82C>T		3_prime_UTR_variant	4/4		XP_047287876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYDE2	ENST00000341460.6 linkuse as main transcript	c.2774C>T	p.Ser925Leu	missense_variant	5/7	5	NM_032184.2	ENSP00000340594.5		Q5VT97-1
SYDE2	ENST00000696556.1 linkuse as main transcript	c.3365C>T	p.Ser1122Leu	missense_variant	5/7			ENSP00000512715.1		A0A8Q3WMH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461568

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000270

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 specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.2774C>T (p.S925L) alteration is located in exon 5 (coding exon 5) of the SYDE2 gene. This alteration results from a C to T substitution at nucleotide position 2774, causing the serine (S) at amino acid position 925 to be replaced by a leucine (L). 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

0.083

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Benign

0.057

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.011

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.9

REVEL

Benign

0.050

Sift

Uncertain

0.0090

Sift4G

Benign

0.25

Polyphen

0.47

Vest4

0.20

MutPred

0.39

Loss of disorder (P = 0.0339);

MVP

0.27

MPC

0.11

ClinPred

0.72

GERP RS

3.5

Varity_R

0.079

gMVP

0.20

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