NM_014258.4:c.3854G>T

Variant names:

• chr20-59868547-C-A
• rs148819194
• NM_014258.4:c.3854G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014258.4(SYCP2):​c.3854G>T​(p.Arg1285Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,451,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. R1285H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SYCP2 NM_014258.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.758
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.050392717).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

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.3854G>T	p.Arg1285Leu	missense	Exon 38 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.3854G>T	p.Arg1285Leu	missense	Exon 38 of 45	ENSP00000350162.2	Q9BX26
	SYCP2	ENST00000371001.6	TSL:1	c.3854G>T	p.Arg1285Leu	missense	Exon 37 of 44	ENSP00000360040.2	Q9BX26
	SYCP2	ENST00000412613.1	TSL:3	c.46+288G>T		intron	N/A	ENSP00000404358.1	A2A340

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000165 AC: 4 AN: 241748 AF XY: 0.00000764

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000941

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000413 AC: 6 AN: 1451094 Hom.: 0 Cov.: 31 AF XY: 0.00000416 AC XY: 3 AN XY: 721632

African (AFR) AF: 0.00 AC: 0 AN: 32814

American (AMR) AF: 0.0000708 AC: 3 AN: 42376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25798

East Asian (EAS) AF: 0.00 AC: 0 AN: 39336

South Asian (SAS) AF: 0.0000239 AC: 2 AN: 83578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108686

Other (OTH) AF: 0.0000167 AC: 1 AN: 59850

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.76
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.014
Sift	Benign	0.19	T
Sift4G	Benign	0.25	T
Polyphen		0.0050	B
Vest4		0.29
MutPred		0.35		Loss of disorder (P = 0.0468)
MVP		0.043
MPC		0.033
ClinPred		0.047	T
GERP RS		-0.15
PromoterAI		-0.016	Neutral
Varity_R		0.039
gMVP		0.090
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs148819194; hg19: chr20-58443602;