Genetic Variant SYCP2L:p.Thr241Met (chr6-10907587-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001040274.3(SYCP2L):c.722C>T(p.Thr241Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,613,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T241A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

SYCP2L
NM_001040274.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

Variant links:

Genes affected

SYCP2L (HGNC:21537): (synaptonemal complex protein 2 like) Predicted to be involved in meiotic nuclear division. Predicted to act upstream of or within negative regulation of cell death. Located in condensed chromosome, centromeric region and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SYCP2L links:

ENSG00000272162 (HGNC:):

ENSG00000272162 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.066458106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCP2L	NM_001040274.3 link	c.722C>T	p.Thr241Met	missense_variant	Exon 10 of 30	ENST00000283141.11	NP_001035364.2	Q5T4T6-1B4DFB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYCP2L	ENST00000283141.11 link	c.722C>T	p.Thr241Met	missense_variant	Exon 10 of 30	1	NM_001040274.3	ENSP00000283141.6	Q5T4T6-1
ENSG00000272162	ENST00000480294.1 link	n.*684C>T		non_coding_transcript_exon_variant	Exon 12 of 19	2		ENSP00000417929.1	F8WBI7
ENSG00000272162	ENST00000480294.1 link	n.*684C>T		3_prime_UTR_variant	Exon 12 of 19	2		ENSP00000417929.1	F8WBI7

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000736

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

249374

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135278

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000602

AC:

AN:

1461442

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000693

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151948

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000414

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.722C>T (p.T241M) alteration is located in exon 10 (coding exon 10) of the SYCP2L gene. This alteration results from a C to T substitution at nucleotide position 722, causing the threonine (T) at amino acid position 241 to be replaced by a methionine (M). 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

0.15

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.061

T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.066

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.3

D;.

REVEL

Benign

0.051

Sift

Benign

0.27

T;.

Sift4G

Benign

0.18

T;T

Polyphen

0.90

P;.

Vest4

0.23

MVP

0.17

MPC

0.24

ClinPred

0.082

GERP RS

2.3

Varity_R

0.027

gMVP

0.41

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