Variant chr20-59865590-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014258.4(SYCP2):c.4441A>G(p.Thr1481Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,603,630 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SYCP2
NM_014258.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.163

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02629146).

BS2

High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYCP2	NM_014258.4 linkuse as main transcript	c.4441A>G	p.Thr1481Ala	missense_variant	43/45	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.4441A>G	p.Thr1481Ala	missense_variant	43/45	1	NM_014258.4	ENSP00000350162.2	Q9BX26
SYCP2	ENST00000371001.6 linkuse as main transcript	c.4441A>G	p.Thr1481Ala	missense_variant	42/44	1		ENSP00000360040.2	Q9BX26
SYCP2	ENST00000412613.1 linkuse as main transcript	c.499A>G	p.Thr167Ala	missense_variant	6/8	3		ENSP00000404358.1	A2A340

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

151908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.0000330

AC:

AN:

242682

Hom.:

AF XY:

0.0000305

AC XY:

AN XY:

131226

show subpopulations

Gnomad AFR exome

AF:

0.000383

Gnomad AMR exome

AF:

0.0000611

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:

0.00

GnomAD4 exome

AF:

0.0000152

AC:

AN:

1451722

Hom.:

Cov.:

AF XY:

0.00000831

AC XY:

AN XY:

721966

show subpopulations

Gnomad4 AFR exome

AF:

0.000336

Gnomad4 AMR exome

AF:

0.0000934

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.000145

AC:

AN:

151908

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74182

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.000269

Hom.:

Bravo

AF:

0.000227

ESP6500AA

AF:

0.000457

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2022

The c.4441A>G (p.T1481A) alteration is located in exon 42 (coding exon 41) of the SYCP2 gene. This alteration results from a A to G substitution at nucleotide position 4441, causing the threonine (T) at amino acid position 1481 to be replaced by an alanine (A). 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

0.083

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.2

DANN

Benign

0.71

DEOGEN2

Benign

0.11

T;T;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.48

.;T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

M;M;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.73

N;N;N

REVEL

Benign

0.013

Sift

Benign

0.053

T;T;T

Sift4G

Benign

0.12

T;T;.

Polyphen

0.017

B;B;.

Vest4

0.11

MVP

0.068

MPC

0.028

ClinPred

0.0041

GERP RS

-1.0

Varity_R

0.047

gMVP

0.031

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

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