Genetic Variant SYCP2:p.Arg1514Cys (chr20-59864364-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_014258.4(SYCP2):c.4540C>T(p.Arg1514Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000106 in 1,599,494 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 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

SYCP2
NM_014258.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.07

Variant links:

Genes affected

SYCP2 (HGNC:11490): (synaptonemal complex protein 2) The synaptonemal complex is a proteinaceous structure that links homologous chromosomes during the prophase of meiosis. The protein encoded by this gene is a major component of the synaptonemal complex and may bind DNA at scaffold attachment regions. The encoded protein requires synaptonemal complex protein 3, but not 1, for inclusion in the synaptonemal complex. [provided by RefSeq, Jul 2008]

SYCP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27966213).

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCP2	NM_014258.4 link	c.4540C>T	p.Arg1514Cys	missense_variant	Exon 45 of 45	ENST00000357552.8	NP_055073.2	Q9BX26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYCP2	ENST00000357552.8 link	c.4540C>T	p.Arg1514Cys	missense_variant	Exon 45 of 45	1	NM_014258.4	ENSP00000350162.2	Q9BX26
SYCP2	ENST00000371001.6 link	c.4540C>T	p.Arg1514Cys	missense_variant	Exon 44 of 44	1		ENSP00000360040.2	Q9BX26
SYCP2	ENST00000412613.1 link	c.598C>T	p.Arg200Cys	missense_variant	Exon 8 of 8	3		ENSP00000404358.1	A2A340

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

150156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000491

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000667

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000124

AC:

AN:

241828

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

131000

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000307

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000685

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000897

AC:

AN:

1449338

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

720774

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:

0.0000477

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000724

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000266

AC:

AN:

150156

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73162

show subpopulations

Gnomad4 AFR

AF:

0.0000491

Gnomad4 AMR

AF:

0.0000667

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4540C>T (p.R1514C) alteration is located in exon 44 (coding exon 43) of the SYCP2 gene. This alteration results from a C to T substitution at nucleotide position 4540, causing the arginine (R) at amino acid position 1514 to be replaced by a cysteine (C). 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

Uncertain

0.34

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;T;T

Eigen

Benign

0.084

Eigen_PC

Benign

0.18

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

.;D;D

M_CAP

Benign

0.048

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M;.

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.4

N;N;D

REVEL

Benign

0.14

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

0.31

B;B;.

Vest4

0.39

MutPred

0.60

Loss of MoRF binding (P = 0.036);Loss of MoRF binding (P = 0.036);.;

MVP

0.13

MPC

0.23

ClinPred

0.95

GERP RS

4.4

Varity_R

0.24

gMVP

0.30

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