6-10891525-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001040274.3(SYCP2L):​c.22G>C​(p.Ala8Pro) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A8S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: SYCP2L NM_001040274.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• premature ovarian failure 24

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ENSG00000272162 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.01986745).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040274.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYCP2L	NM_001040274.3	MANE Select	c.22G>C	p.Ala8Pro	missense	Exon 2 of 30	NP_001035364.2	Q5T4T6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYCP2L	ENST00000283141.11	TSL:1 MANE Select	c.22G>C	p.Ala8Pro	missense	Exon 2 of 30	ENSP00000283141.6	Q5T4T6-1
	ENSG00000272162	ENST00000480294.1	TSL:2	n.113G>C		non_coding_transcript_exon	Exon 4 of 19	ENSP00000417929.1	F8WBI7
	SYCP2L	ENST00000341041.8	TSL:2	n.22G>C		non_coding_transcript_exon	Exon 2 of 30	ENSP00000340320.4	Q5T4T6-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.14
DANN	Benign	0.28
DEOGEN2	Benign	0.00034	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00049	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.5	N
PhyloP100		-0.94
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.028
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.053
MutPred		0.18		Gain of loop (P = 0.0097)
MVP		0.014
MPC		0.16
ClinPred		0.055	T
GERP RS		-0.63
PromoterAI		0.0090	Neutral
Varity_R		0.036
gMVP		0.099
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1780171731; hg19: chr6-10891758;