rs1451260409

Variant names:

• chr2-186828330-T-A
• rs1451260409
• NM_182521.3:c.1556A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-186828330-T-A
• chr2-186828330-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182521.3(ZSWIM2):​c.1556A>T​(p.His519Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.0000066 (0 hom., cov: 32)
• Consequence: ZSWIM2 NM_182521.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.253

Genes affected

ZSWIM2 (HGNC:30990): (zinc finger SWIM-type containing 2) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in apoptotic process and protein polyubiquitination. Predicted to act upstream of or within positive regulation of extrinsic apoptotic signaling pathway via death domain receptors. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09769806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM2	NM_182521.3	c.1556A>T	p.His519Leu	missense_variant	Exon 9 of 9	ENST00000295131.3	NP_872327.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM2	ENST00000295131.3	c.1556A>T	p.His519Leu	missense_variant	Exon 9 of 9	1	NM_182521.3	ENSP00000295131.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74292

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.3
DANN	Benign	0.73
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.015
Sift	Benign	0.051	T
Sift4G	Uncertain	0.042	D
Polyphen		0.12	B
Vest4		0.26
MutPred		0.45		Gain of ubiquitination at K520 (P = 0.0432);
MVP		0.072
MPC		0.010
ClinPred		0.036	T
GERP RS		1.0
Varity_R		0.072
gMVP		0.19

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: rs1451260409; hg19: chr2-187693057;