chr20-59865626-C-G

Variant names:

• chr20-59865626-C-G
• rs539397918
• NM_014258.4:c.4405G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014258.4(SYCP2):​c.4405G>C​(p.Ala1469Pro) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1469T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYCP2 NM_014258.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• spermatogenic failure 1

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056801558).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014258.4. 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
	SYCP2	NM_014258.4	MANE Select	c.4405G>C	p.Ala1469Pro	missense	Exon 43 of 45	NP_055073.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYCP2	ENST00000357552.8	TSL:1 MANE Select	c.4405G>C	p.Ala1469Pro	missense	Exon 43 of 45	ENSP00000350162.2	Q9BX26
	SYCP2	ENST00000371001.6	TSL:1	c.4405G>C	p.Ala1469Pro	missense	Exon 42 of 44	ENSP00000360040.2	Q9BX26
	SYCP2	ENST00000412613.1	TSL:3	c.463G>C	p.Ala155Pro	missense	Exon 6 of 8	ENSP00000404358.1	A2A340

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.3
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.0080
Sift	Benign	0.12	T
Sift4G	Benign	0.091	T
Polyphen		0.17	B
Vest4		0.23
MutPred		0.39		Gain of disorder (P = 0.05)
MVP		0.10
MPC		0.041
ClinPred		0.20	T
GERP RS		3.6
Varity_R		0.087
gMVP		0.17
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs539397918; hg19: chr20-58440681;