Variant 1-109467119-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001040709.2(SYPL2):c.115A>G(p.Lys39Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000013 in 1,543,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SYPL2
NM_001040709.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

Variant links:

Genes affected

SYPL2 (HGNC:27638): (synaptophysin like 2) Involved in substantia nigra development. Predicted to be integral component of membrane. Predicted to be active in synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

SYPL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYPL2	NM_001040709.2 linkuse as main transcript	c.115A>G	p.Lys39Glu	missense_variant	2/6	ENST00000369872.4	NP_001035799.1	Q5VXT5-1
SYPL2	XM_011541283.3 linkuse as main transcript	c.115A>G	p.Lys39Glu	missense_variant	2/7		XP_011539585.1
SYPL2	XM_011541284.3 linkuse as main transcript	c.115A>G	p.Lys39Glu	missense_variant	2/6		XP_011539586.1
SYPL2	XM_011541285.2 linkuse as main transcript	c.115A>G	p.Lys39Glu	missense_variant	2/5		XP_011539587.1	B4DYR7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYPL2	ENST00000369872.4 linkuse as main transcript	c.115A>G	p.Lys39Glu	missense_variant	2/6	1	NM_001040709.2	ENSP00000358888.3		Q5VXT5-1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151838

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.19e-7

AC:

AN:

1391640

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

686534

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000281

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151838

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74136

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

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

Aug 15, 2024

The c.115A>G (p.K39E) alteration is located in exon 2 (coding exon 2) of the SYPL2 gene. This alteration results from a A to G substitution at nucleotide position 115, causing the lysine (K) at amino acid position 39 to be replaced by a glutamic acid (E). 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

0.99

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

M_CAP

Pathogenic

0.55

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.3

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.33

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.0060

Polyphen

0.79

Vest4

0.70

MutPred

0.64

Loss of methylation at K39 (P = 0.0029);

MVP

0.35

MPC

0.84

ClinPred

0.97

GERP RS

5.0

Varity_R

0.53

gMVP

0.84

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