Variant chr20-59865818-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_014258.4(SYCP2):c.4368C>T(p.Ser1456Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 1,431,402 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 23 hom. )

Consequence

SYCP2
NM_014258.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.50

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]

SYCP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 20-59865818-G-A is Benign according to our data. Variant chr20-59865818-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2498889.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.5 with no splicing effect.

BS2

High AC in GnomAd4 at 553 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYCP2	NM_014258.4 linkuse as main transcript	c.4368C>T	p.Ser1456Ser	synonymous_variant	42/45	ENST00000357552.8	NP_055073.2	Q9BX26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SYCP2	ENST00000357552.8 linkuse as main transcript	c.4368C>T	p.Ser1456Ser	synonymous_variant	42/45	1	NM_014258.4	ENSP00000350162.2	Q9BX26
SYCP2	ENST00000371001.6 linkuse as main transcript	c.4368C>T	p.Ser1456Ser	synonymous_variant	41/44	1		ENSP00000360040.2	Q9BX26
SYCP2	ENST00000412613.1 linkuse as main transcript	c.426C>T	p.Ser142Ser	synonymous_variant	5/8	3		ENSP00000404358.1	A2A340

Frequencies

GnomAD3 genomes

AF:

0.00366

AC:

553

AN:

151208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000920

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00171

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00242

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00666

Gnomad OTH

AF:

0.00241

GnomAD3 exomes

AF:

0.00329

AC:

631

AN:

191826

Hom.:

AF XY:

0.00326

AC XY:

346

AN XY:

106074

show subpopulations

Gnomad AFR exome

AF:

0.000633

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.000973

Gnomad EAS exome

AF:

0.0000807

Gnomad SAS exome

AF:

0.000345

Gnomad FIN exome

AF:

0.00230

Gnomad NFE exome

AF:

0.00583

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00513

AC:

6567

AN:

1280078

Hom.:

Cov.:

AF XY:

0.00511

AC XY:

3239

AN XY:

633772

show subpopulations

Gnomad4 AFR exome

AF:

0.000914

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.000948

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000327

Gnomad4 FIN exome

AF:

0.00229

Gnomad4 NFE exome

AF:

0.00615

Gnomad4 OTH exome

AF:

0.00335

GnomAD4 genome

AF:

0.00365

AC:

553

AN:

151324

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

223

AN XY:

73922

show subpopulations

Gnomad4 AFR

AF:

0.000918

Gnomad4 AMR

AF:

0.00171

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00242

Gnomad4 NFE

AF:

0.00666

Gnomad4 OTH

AF:

0.00239

Alfa

AF:

0.00478

Hom.:

Bravo

AF:

0.00370

Asia WGS

AF:

0.000587

AC:

AN:

3420

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SYCP2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 22, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

SYCP2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.5

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over