6-10894154-G-A

Variant names:

• chr6-10894154-G-A
• NM_001040274.3:c.286G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040274.3(SYCP2L):​c.286G>A​(p.Gly96Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,184 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. G96D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SYCP2L NM_001040274.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46

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]

ENSG00000272162 (HGNC:):

ACMG classification

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=0.16083157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCP2L	NM_001040274.3	c.286G>A	p.Gly96Ser	missense_variant	Exon 4 of 30	ENST00000283141.11	NP_001035364.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYCP2L	ENST00000283141.11	c.286G>A	p.Gly96Ser	missense_variant	Exon 4 of 30	1	NM_001040274.3	ENSP00000283141.6
ENSG00000272162	ENST00000480294.1	n.*248G>A		non_coding_transcript_exon_variant	Exon 6 of 19	2		ENSP00000417929.1
ENSG00000272162	ENST00000480294.1	n.*248G>A		3_prime_UTR_variant	Exon 6 of 19	2		ENSP00000417929.1
SYCP2L	ENST00000341041.8	n.286G>A		non_coding_transcript_exon_variant	Exon 4 of 30	2		ENSP00000340320.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461184 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726840

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.286G>A (p.G96S) alteration is located in exon 4 (coding exon 4) of the SYCP2L gene. This alteration results from a G to A substitution at nucleotide position 286, causing the glycine (G) at amino acid position 96 to be replaced by a serine (S). 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	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0041	T;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.050
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.11
Sift	Benign	0.18	T;.
Sift4G	Benign	0.23	T;T
Polyphen		0.90	P;.
Vest4		0.064
MutPred		0.38		Gain of relative solvent accessibility (P = 0.09);.;
MVP		0.25
MPC		0.15
ClinPred		0.63	D
GERP RS		4.7
Varity_R		0.10
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-10894387;