6-10959925-G-C

Variant names:

• chr6-10959925-G-C
• rs6918936
• NM_001040274.3:c.2255+1050G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040274.3(SYCP2L):​c.2255+1050G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 150,654 control chromosomes in the GnomAD database, including 23,665 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23665 hom., cov: 29)
• Consequence: SYCP2L NM_001040274.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 18 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

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.2255+1050G>C		intron	N/A	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.2255+1050G>C		intron	N/A	ENSP00000283141.6	Q5T4T6-1
	SYCP2L	ENST00000341041.8	TSL:2	n.*1433+1050G>C		intron	N/A	ENSP00000340320.4	Q5T4T6-2

Frequencies

GnomAD3 genomes AF: 0.549 AC: 82715 AN: 150548 Hom.: 23616 Cov.: 29

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.535

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.550 AC: 82819 AN: 150654 Hom.: 23665 Cov.: 29 AF XY: 0.558 AC XY: 40965 AN XY: 73440

African (AFR) AF: 0.623 AC: 25583 AN: 41048

American (AMR) AF: 0.635 AC: 9608 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2008 AN: 3460

East Asian (EAS) AF: 0.909 AC: 4656 AN: 5120

South Asian (SAS) AF: 0.712 AC: 3418 AN: 4802

European-Finnish (FIN) AF: 0.499 AC: 5011 AN: 10044

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.457 AC: 30947 AN: 67748

Other (OTH) AF: 0.538 AC: 1126 AN: 2094

Alfa AF: 0.496 Hom.: 2308

Bravo AF: 0.563

Asia WGS AF: 0.775 AC: 2695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.51
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs6918936; hg19: chr6-10960158;