chr20-59865441-A-G

Position:

• chr20-59865441-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014258.4(SYCP2):​c.4462T>C​(p.Cys1488Arg) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYCP2 NM_014258.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.240

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.076967984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYCP2	NM_014258.4	c.4462T>C	p.Cys1488Arg	missense_variant	44/45	ENST00000357552.8	NP_055073.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYCP2	ENST00000357552.8	c.4462T>C	p.Cys1488Arg	missense_variant	44/45	1	NM_014258.4	ENSP00000350162.2
SYCP2	ENST00000371001.6	c.4462T>C	p.Cys1488Arg	missense_variant	43/44	1		ENSP00000360040.2
SYCP2	ENST00000412613.1	c.520T>C	p.Cys174Arg	missense_variant	7/8	3		ENSP00000404358.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 05, 2024

The c.4462T>C (p.C1488R) alteration is located in exon 43 (coding exon 42) of the SYCP2 gene. This alteration results from a T to C substitution at nucleotide position 4462, causing the cysteine (C) at amino acid position 1488 to be replaced by an arginine (R). 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	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.66
DEOGEN2	Benign	0.17	T;T;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.41	.;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.077	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.9	N;N;D
REVEL	Benign	0.083
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.35	T;T;.
Polyphen		0.59	P;P;.
Vest4		0.24
MutPred		0.43		Loss of catalytic residue at L1489 (P = 0.0085);Loss of catalytic residue at L1489 (P = 0.0085);.;
MVP		0.27
MPC		0.040
ClinPred		0.35	T
GERP RS		0.23
Varity_R		0.28
gMVP		0.072

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-58440496;