2-186828577-T-C

Variant names:

• chr2-186828577-T-C
• rs201343857
• NM_182521.3:c.1309A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_182521.3(ZSWIM2):​c.1309A>G​(p.Arg437Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000961 in 1,612,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000099 (0 hom.)
• Consequence: ZSWIM2 NM_182521.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.532
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019109935).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182521.3. 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
	ZSWIM2	NM_182521.3	MANE Select	c.1309A>G	p.Arg437Gly	missense	Exon 9 of 9	NP_872327.2	Q8NEG5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM2	ENST00000295131.3	TSL:1 MANE Select	c.1309A>G	p.Arg437Gly	missense	Exon 9 of 9	ENSP00000295131.2	Q8NEG5

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000140 AC: 35 AN: 249766 AF XY: 0.000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000378

Gnomad ASJ exome AF: 0.000796

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000993 AC: 145 AN: 1460788 Hom.: 0 Cov.: 32 AF XY: 0.0000881 AC XY: 64 AN XY: 726602

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.000314 AC: 14 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.000728 AC: 19 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000918 AC: 102 AN: 1111382

Other (OTH) AF: 0.000166 AC: 10 AN: 60334

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74328

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000159 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.000124 AC: 15

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.53
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.021
Sift	Benign	0.059	T
Sift4G	Benign	0.28	T
Polyphen		0.0010	B
Vest4		0.082
MVP		0.014
MPC		0.0098
ClinPred		0.021	T
GERP RS		0.082
Varity_R		0.12
gMVP		0.29
Mutation Taster		=86/14	polymorphism

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: rs201343857; hg19: chr2-187693304;