20-59868547-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_014258.4(SYCP2):​c.3854G>A​(p.Arg1285His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000799 in 1,602,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

SYCP2
NM_014258.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.758
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYCP2NM_014258.4 linkc.3854G>A p.Arg1285His missense_variant Exon 38 of 45 ENST00000357552.8 NP_055073.2 Q9BX26

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYCP2ENST00000357552.8 linkc.3854G>A p.Arg1285His missense_variant Exon 38 of 45 1 NM_014258.4 ENSP00000350162.2 Q9BX26
SYCP2ENST00000371001.6 linkc.3854G>A p.Arg1285His missense_variant Exon 37 of 44 1 ENSP00000360040.2 Q9BX26
SYCP2ENST00000412613.1 linkc.46+288G>A intron_variant Intron 1 of 7 3 ENSP00000404358.1 A2A340

Frequencies

GnomAD3 genomes
AF:
0.000231
AC:
35
AN:
151500
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000750
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000660
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000947
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000112
AC:
27
AN:
241748
Hom.:
0
AF XY:
0.0000841
AC XY:
11
AN XY:
130842
show subpopulations
Gnomad AFR exome
AF:
0.00126
Gnomad AMR exome
AF:
0.0000314
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000112
Gnomad SAS exome
AF:
0.0000355
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000270
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000641
AC:
93
AN:
1451094
Hom.:
0
Cov.:
31
AF XY:
0.0000568
AC XY:
41
AN XY:
721632
show subpopulations
Gnomad4 AFR exome
AF:
0.00104
Gnomad4 AMR exome
AF:
0.0000236
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000508
Gnomad4 SAS exome
AF:
0.0000120
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000442
Gnomad4 OTH exome
AF:
0.0000835
GnomAD4 genome
AF:
0.000231
AC:
35
AN:
151618
Hom.:
0
Cov.:
32
AF XY:
0.000283
AC XY:
21
AN XY:
74090
show subpopulations
Gnomad4 AFR
AF:
0.000748
Gnomad4 AMR
AF:
0.0000659
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000947
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000590
Hom.:
0
Bravo
AF:
0.000306
ESP6500AA
AF:
0.000908
AC:
4
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000115
AC:
14

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 29, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3854G>A (p.R1285H) alteration is located in exon 37 (coding exon 36) of the SYCP2 gene. This alteration results from a G to A substitution at nucleotide position 3854, causing the arginine (R) at amino acid position 1285 to be replaced by a histidine (H). 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
-0.63
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T;T
Eigen
Benign
-0.70
Eigen_PC
Benign
-0.69
FATHMM_MKL
Benign
0.085
N
LIST_S2
Benign
0.59
.;T
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.019
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;L
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-1.0
N;N
REVEL
Benign
0.015
Sift
Benign
0.055
T;T
Sift4G
Benign
0.18
T;T
Polyphen
0.055
B;B
Vest4
0.36
MVP
0.043
MPC
0.18
ClinPred
0.021
T
GERP RS
-0.15
Varity_R
0.027
gMVP
0.089

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.21
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.21
Position offset: 21

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.

Other links and lift over

dbSNP: rs148819194; hg19: chr20-58443602; COSMIC: COSV62767551; API