20-59867718-C-T

Variant names:

• chr20-59867718-C-T
• rs747228898
• NM_014258.4:c.4118G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_014258.4(SYCP2):​c.4118G>A​(p.Arg1373Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYCP2 NM_014258.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.393

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025037974).
• BP6: Variant 20-59867718-C-T is Benign according to our data. Variant chr20-59867718-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3451754.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCP2	NM_014258.4	c.4118G>A	p.Arg1373Lys	missense_variant	Exon 39 of 45	ENST00000357552.8	NP_055073.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYCP2	ENST00000357552.8	c.4118G>A	p.Arg1373Lys	missense_variant	Exon 39 of 45	1	NM_014258.4	ENSP00000350162.2
SYCP2	ENST00000371001.6	c.4118G>A	p.Arg1373Lys	missense_variant	Exon 38 of 44	1		ENSP00000360040.2
SYCP2	ENST00000412613.1	c.176G>A	p.Arg59Lys	missense_variant	Exon 2 of 8	3		ENSP00000404358.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 247928 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134130

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Aug 11, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.2
DANN	Benign	0.43
DEOGEN2	Benign	0.070	T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.36	.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.025	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.060	N;N;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.23	N;N;N
REVEL	Benign	0.048
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;.
Polyphen		0.0	B;B;.
Vest4		0.11
MutPred		0.36		Gain of methylation at R1373 (P = 0.0153);Gain of methylation at R1373 (P = 0.0153);.;
MVP		0.043
MPC		0.028
ClinPred		0.022	T
GERP RS		0.41
Varity_R		0.044
gMVP		0.050

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

Other links and lift over

dbSNP: rs747228898; hg19: chr20-58442773;