rs2502601

Variant names:

• chr6-158096276-A-G
• rs2502601
• NM_003898.4:c.4403A>G

Variant summary

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

The NM_003898.4(SYNJ2):​c.4403A>G​(p.Glu1468Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 1,613,888 control chromosomes in the GnomAD database, including 213,305 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.53 (21292 hom., cov: 33)
  • Exomes 𝑓: 0.51 (192013 hom.)
• Consequence: SYNJ2 NM_003898.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 38 publications found

Genes affected

SYNJ2 (HGNC:11504): (synaptojanin 2) The gene is a member of the inositol-polyphosphate 5-phosphatase family. The encoded protein interacts with the ras-related C3 botulinum toxin substrate 1, which causes translocation of the encoded protein to the plasma membrane where it inhibits clathrin-mediated endocytosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.2998245E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003898.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ2	NM_003898.4	MANE Select	c.4403A>G	p.Glu1468Gly	missense	Exon 27 of 27	NP_003889.1
	SYNJ2	NM_001178088.2		c.3692A>G	p.Glu1231Gly	missense	Exon 26 of 26	NP_001171559.1
	SYNJ2	NM_001410947.1		c.*686A>G		3_prime_UTR	Exon 28 of 28	NP_001397876.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ2	ENST00000355585.9	TSL:1 MANE Select	c.4403A>G	p.Glu1468Gly	missense	Exon 27 of 27	ENSP00000347792.4
	SYNJ2	ENST00000638626.1	TSL:1	c.3692A>G	p.Glu1231Gly	missense	Exon 26 of 26	ENSP00000492369.1
	SYNJ2	ENST00000367122.6	TSL:1	c.2432A>G	p.Glu811Gly	missense	Exon 14 of 14	ENSP00000356089.3

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79864 AN: 152012 Hom.: 21275 Cov.: 33

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.518

GnomAD2 exomes AF: 0.503 AC: 126092 AN: 250752 AF XY: 0.507

Gnomad AFR exome AF: 0.595

Gnomad AMR exome AF: 0.323

Gnomad ASJ exome AF: 0.467

Gnomad EAS exome AF: 0.575

Gnomad FIN exome AF: 0.544

Gnomad NFE exome AF: 0.514

Gnomad OTH exome AF: 0.492

GnomAD4 exome AF: 0.510 AC: 745060 AN: 1461758 Hom.: 192013 Cov.: 60 AF XY: 0.511 AC XY: 371291 AN XY: 727180

African (AFR) AF: 0.599 AC: 20038 AN: 33478

American (AMR) AF: 0.327 AC: 14602 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 12161 AN: 26136

East Asian (EAS) AF: 0.508 AC: 20176 AN: 39700

South Asian (SAS) AF: 0.551 AC: 47527 AN: 86254

European-Finnish (FIN) AF: 0.544 AC: 29012 AN: 53364

Middle Eastern (MID) AF: 0.453 AC: 2612 AN: 5768

European-Non Finnish (NFE) AF: 0.510 AC: 567347 AN: 1111954

Other (OTH) AF: 0.523 AC: 31585 AN: 60396

GnomAD4 genome AF: 0.525 AC: 79913 AN: 152130 Hom.: 21292 Cov.: 33 AF XY: 0.525 AC XY: 39056 AN XY: 74384

African (AFR) AF: 0.591 AC: 24535 AN: 41506

American (AMR) AF: 0.384 AC: 5869 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1645 AN: 3468

East Asian (EAS) AF: 0.565 AC: 2914 AN: 5158

South Asian (SAS) AF: 0.570 AC: 2747 AN: 4822

European-Finnish (FIN) AF: 0.545 AC: 5765 AN: 10582

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.509 AC: 34583 AN: 67984

Other (OTH) AF: 0.516 AC: 1090 AN: 2112

Alfa AF: 0.508 Hom.: 68999

Bravo AF: 0.516

TwinsUK AF: 0.515 AC: 1909

ALSPAC AF: 0.513 AC: 1979

ESP6500AA AF: 0.582 AC: 2563

ESP6500EA AF: 0.509 AC: 4379

ExAC AF: 0.513 AC: 62317

Asia WGS AF: 0.571 AC: 1988 AN: 3478

EpiCase AF: 0.501

EpiControl AF: 0.498

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.71
DANN	Benign	0.88
DEOGEN2	Benign	0.23	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.000013	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.042
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.15
Sift	Benign	0.82	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.033
MPC		0.22
ClinPred		0.0046	T
GERP RS		0.080
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.035
gMVP		0.061
Mutation Taster		=99/1	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: rs2502601; hg19: chr6-158517308; COSMIC: COSV62895621; COSMIC: COSV62895621;