1-109473756-A-G

Variant names:

• chr1-109473756-A-G
• rs2359653
• NM_001040709.2:c.130-1825A>G

Variant summary

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

The NM_001040709.2(SYPL2):​c.130-1825A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 151,854 control chromosomes in the GnomAD database, including 35,413 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 0.68 (35413 hom., cov: 30)
• Consequence: SYPL2 NM_001040709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.92
• Publications: 7 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040709.2. 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
	SYPL2	NM_001040709.2	MANE Select	c.130-1825A>G		intron	N/A	NP_001035799.1	Q5VXT5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYPL2	ENST00000369872.4	TSL:1 MANE Select	c.130-1825A>G		intron	N/A	ENSP00000358888.3	Q5VXT5-1
	SYPL2	ENST00000950144.1		c.214-1825A>G		intron	N/A	ENSP00000620203.1
	SYPL2	ENST00000880157.1		c.130-1825A>G		intron	N/A	ENSP00000550216.1

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102507 AN: 151736 Hom.: 35388 Cov.: 30

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.676 AC: 102581 AN: 151854 Hom.: 35413 Cov.: 30 AF XY: 0.678 AC XY: 50285 AN XY: 74198

African (AFR) AF: 0.549 AC: 22729 AN: 41416

American (AMR) AF: 0.786 AC: 12002 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2782 AN: 3466

East Asian (EAS) AF: 0.958 AC: 4952 AN: 5168

South Asian (SAS) AF: 0.727 AC: 3492 AN: 4802

European-Finnish (FIN) AF: 0.666 AC: 7014 AN: 10532

Middle Eastern (MID) AF: 0.709 AC: 207 AN: 292

European-Non Finnish (NFE) AF: 0.696 AC: 47257 AN: 67894

Other (OTH) AF: 0.720 AC: 1521 AN: 2112

Alfa AF: 0.573 Hom.: 1761

Bravo AF: 0.684

Asia WGS AF: 0.806 AC: 2800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.13
DANN	Benign	0.21
PhyloP100		-3.9
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2359653;

hg19: chr1-110016378;