Genetic Variant SYCP2L:p.Thr188Ile (chr6-10902885-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040274.3(SYCP2L):c.563C>T(p.Thr188Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SYCP2L
NM_001040274.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23690352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCP2L	NM_001040274.3 link	c.563C>T	p.Thr188Ile	missense_variant	Exon 8 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.563C>T	p.Thr188Ile	missense_variant	Exon 8 of 30	1	NM_001040274.3	ENSP00000283141.6	Q5T4T6-1
ENSG00000272162	ENST00000480294.1 link	n.*525C>T		non_coding_transcript_exon_variant	Exon 10 of 19	2		ENSP00000417929.1	F8WBI7
ENSG00000272162	ENST00000480294.1 link	n.*525C>T		3_prime_UTR_variant	Exon 10 of 19	2		ENSP00000417929.1	F8WBI7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249452

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.563C>T (p.T188I) alteration is located in exon 8 (coding exon 8) of the SYCP2L gene. This alteration results from a C to T substitution at nucleotide position 563, causing the threonine (T) at amino acid position 188 to be replaced by an isoleucine (I). 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

0.26

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

0.041

Eigen_PC

Benign

-0.057

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.0

D;.

REVEL

Benign

0.20

Sift

Uncertain

0.0050

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.72

MutPred

0.32

Gain of ubiquitination at K187 (P = 0.072);.;

MVP

0.44

MPC

0.60

ClinPred

0.98

GERP RS

4.8

Varity_R

0.26

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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