rs2286751

Variant names:

• chr19-56782026-A-C
• rs2286751
• NM_001387356.1:c.666T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-56782026-A-C
• chr19-56782026-A-G
• chr19-56782026-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001369773.1(ZIM2):​c.666T>G​(p.Ser222Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 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: not found (cov: 32)
• Consequence: ZIM2 NM_001369773.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 25 publications found

Genes affected

ZIM2 (HGNC:12875): (zinc finger imprinted 2) In human, ZIM2 and PEG3 (GeneID:5178) are two distinct genes that share a set of 5' exons and have a common promoter, and both genes are paternally expressed. Alternative splicing events connect the shared exons either with the remaining 4 exons unique to ZIM2, or with the remaining 2 exons unique to PEG3. This is in contrast to mouse and cow, where ZIM2 and PEG3 genes do not share exons in common, and the imprinting status of ZIM2 is also not conserved amongst mammals. Additional 5' alternatively spliced transcripts encoding the same protein have been found for the human ZIM2 gene. [provided by RefSeq, Oct 2010]

ENSG00000286125 (HGNC:):

ZIM2-AS1 (HGNC:51304): (ZIM2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058559).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369773.1. 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
	ZIM2	NM_001387356.1	MANE Select	c.666T>G	p.Ser222Arg	missense	Exon 11 of 13	NP_001374285.1
	ZIM2	NM_001369773.1		c.666T>G	p.Ser222Arg	missense	Exon 10 of 12	NP_001356702.1
	ZIM2	NM_001369774.1		c.666T>G	p.Ser222Arg	missense	Exon 10 of 12	NP_001356703.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZIM2	ENST00000629319.3	TSL:5 MANE Select	c.666T>G	p.Ser222Arg	missense	Exon 11 of 13	ENSP00000486502.2
	ZIM2	ENST00000593711.6	TSL:1	c.573T>G	p.Ser191Arg	missense	Exon 9 of 11	ENSP00000472306.1
	ZIM2	ENST00000601070.5	TSL:1	c.573T>G	p.Ser191Arg	missense	Exon 9 of 11	ENSP00000470326.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.90
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.52	N
PhyloP100		-2.2
Sift4G	Benign	0.85	T
Polyphen		0.0050	B
Vest4		0.22
MutPred		0.44		Loss of phosphorylation at S191 (P = 0.038)
MVP		0.014
ClinPred		0.49	T
GERP RS		1.8
Varity_R		0.048
gMVP		0.025
Mutation Taster		=100/0	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: rs2286751; hg19: chr19-57293394;