Genetic Variant SYPL2:p.Arg27Cys (chr1-109467083-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001040709.2(SYPL2):c.79C>T(p.Arg27Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,545,232 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 0.000079 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

SYPL2
NM_001040709.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.35703146).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040709.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYPL2	NM_001040709.2	MANE Select	c.79C>T	p.Arg27Cys	missense	Exon 2 of 6	NP_001035799.1	Q5VXT5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYPL2	ENST00000369872.4	TSL:1 MANE Select	c.79C>T	p.Arg27Cys	missense	Exon 2 of 6	ENSP00000358888.3	Q5VXT5-1
SYPL2	ENST00000950144.1		c.163C>T	p.Arg55Cys	missense	Exon 2 of 6	ENSP00000620203.1
SYPL2	ENST00000880157.1		c.79C>T	p.Arg27Cys	missense	Exon 2 of 5	ENSP00000550216.1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000134

AC:

AN:

141368

AF XY:

0.000118

show subpopulations

Gnomad AFR exome

AF:

0.000149

Gnomad AMR exome

AF:

0.000163

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000251

Gnomad OTH exome

AF:

0.000242

GnomAD4 exome

AF:

0.000187

AC:

261

AN:

1393072

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

124

AN XY:

687212

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31570

American (AMR)

AF:

0.000168

AC:

AN:

35622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25118

East Asian (EAS)

AF:

0.00

AC:

AN:

35726

South Asian (SAS)

AF:

0.00

AC:

AN:

79034

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44668

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5484

European-Non Finnish (NFE)

AF:

0.000227

AC:

245

AN:

1078012

Other (OTH)

AF:

0.000156

AC:

AN:

57838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68016

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000147

AC:

ExAC

AF:

0.0000550

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.36

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

2.4

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.10

Sift

Uncertain

0.015

Sift4G

Uncertain

0.0080

Polyphen

0.99

Vest4

0.33

MVP

0.56

MPC

0.35

ClinPred

0.20

GERP RS

5.0

Varity_R

0.31

gMVP

0.80

Mutation Taster

=68/32

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over