6-10891525-G-T

Variant names:

• chr6-10891525-G-T
• rs1780171731
• NM_001040274.3:c.22G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001040274.3(SYCP2L):​c.22G>T​(p.Ala8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: SYCP2L NM_001040274.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.936

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 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=0.026191592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCP2L	NM_001040274.3	c.22G>T	p.Ala8Ser	missense_variant	Exon 2 of 30	ENST00000283141.11	NP_001035364.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYCP2L	ENST00000283141.11	c.22G>T	p.Ala8Ser	missense_variant	Exon 2 of 30	1	NM_001040274.3	ENSP00000283141.6
ENSG00000272162	ENST00000480294.1	n.113G>T		non_coding_transcript_exon_variant	Exon 4 of 19	2		ENSP00000417929.1
SYCP2L	ENST00000341041.8	n.22G>T		non_coding_transcript_exon_variant	Exon 2 of 30	2		ENSP00000340320.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 01, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.22G>T (p.A8S) alteration is located in exon 2 (coding exon 2) of the SYCP2L gene. This alteration results from a G to T substitution at nucleotide position 22, causing the alanine (A) at amino acid position 8 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	0.087
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.61
DANN	Benign	0.68
DEOGEN2	Benign	0.00053	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.27	T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.026	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.90	N;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.25	N;.
REVEL	Benign	0.020
Sift	Benign	0.051	T;.
Sift4G	Benign	0.28	T;T
Polyphen		0.0	B;.
Vest4		0.038
MutPred		0.14		Gain of loop (P = 0.0166);.;
MVP		0.014
MPC		0.11
ClinPred		0.077	T
GERP RS		-0.63
Varity_R		0.043
gMVP		0.12

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

Other links and lift over

dbSNP: rs1780171731; hg19: chr6-10891758;