rs62623713

Positions:

• chr1-109476817-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040709.2(SYPL2):​c.296A>G​(p.Glu99Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 1,614,138 control chromosomes in the GnomAD database, including 2,873 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.047 (205 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2668 hom.)
• Consequence: SYPL2 NM_001040709.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.857

Genes affected

SYPL2 (HGNC:27638): (synaptophysin like 2) Involved in substantia nigra development. Predicted to be integral component of membrane. Predicted to be active in synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

SYPL2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018308759).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYPL2	NM_001040709.2	c.296A>G	p.Glu99Gly	missense_variant	4/6	ENST00000369872.4	NP_001035799.1
SYPL2	XM_011541283.3	c.296A>G	p.Glu99Gly	missense_variant	4/7		XP_011539585.1
SYPL2	XM_011541284.3	c.296A>G	p.Glu99Gly	missense_variant	4/6		XP_011539586.1
SYPL2	XM_011541285.2	c.296A>G	p.Glu99Gly	missense_variant	4/5		XP_011539587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYPL2	ENST00000369872.4	c.296A>G	p.Glu99Gly	missense_variant	4/6	1	NM_001040709.2	ENSP00000358888.3
SYPL2	ENST00000475497.1	n.506A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 7081 AN: 152158 Hom.: 205 Cov.: 32

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0556

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0641

Gnomad OTH AF: 0.0307

GnomAD3 exomes AF: 0.0478 AC: 11914 AN: 249458 Hom.: 402 AF XY: 0.0499 AC XY: 6753 AN XY: 135358

Gnomad AFR exome AF: 0.0263

Gnomad AMR exome AF: 0.0130

Gnomad ASJ exome AF: 0.0177

Gnomad EAS exome AF: 0.00150

Gnomad SAS exome AF: 0.0572

Gnomad FIN exome AF: 0.0731

Gnomad NFE exome AF: 0.0641

Gnomad OTH exome AF: 0.0444

GnomAD4 exome AF: 0.0560 AC: 81838 AN: 1461862 Hom.: 2668 Cov.: 32 AF XY: 0.0564 AC XY: 41022 AN XY: 727222

Gnomad4 AFR exome AF: 0.0267

Gnomad4 AMR exome AF: 0.0134

Gnomad4 ASJ exome AF: 0.0165

Gnomad4 EAS exome AF: 0.000756

Gnomad4 SAS exome AF: 0.0556

Gnomad4 FIN exome AF: 0.0716

Gnomad4 NFE exome AF: 0.0614

Gnomad4 OTH exome AF: 0.0486

GnomAD4 genome AF: 0.0465 AC: 7087 AN: 152276 Hom.: 205 Cov.: 32 AF XY: 0.0477 AC XY: 3550 AN XY: 74442

Gnomad4 AFR AF: 0.0265

Gnomad4 AMR AF: 0.0221

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.0556

Gnomad4 FIN AF: 0.0778

Gnomad4 NFE AF: 0.0641

Gnomad4 OTH AF: 0.0304

Alfa AF: 0.0565 Hom.: 395

Bravo AF: 0.0399

TwinsUK AF: 0.0580 AC: 215

ALSPAC AF: 0.0592 AC: 228

ESP6500AA AF: 0.0267 AC: 109

ESP6500EA AF: 0.0567 AC: 475

ExAC AF: 0.0513 AC: 6203

Asia WGS AF: 0.0400 AC: 140 AN: 3478

EpiCase AF: 0.0541

EpiControl AF: 0.0505

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.023
Sift	Benign	0.57	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.092
MPC		0.24
ClinPred		0.0030	T
GERP RS		3.3
Varity_R		0.063
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs62623713; hg19: chr1-110019439;