chr19-56782026-A-C

Variant names:

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

Variant summary

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

The NM_001387356.1(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_001387356.1 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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIM2	NM_001387356.1	c.666T>G	p.Ser222Arg	missense_variant	Exon 11 of 13	ENST00000629319.3	NP_001374285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZIM2	ENST00000629319.3	c.666T>G	p.Ser222Arg	missense_variant	Exon 11 of 13	5	NM_001387356.1	ENSP00000486502.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T;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;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.52	N;N;N;N
PhyloP100		-2.2
Sift4G	Benign	0.85	T;T;T;T
Polyphen		0.0050	B;B;B;B
Vest4		0.22
MutPred		0.44		Loss of phosphorylation at S191 (P = 0.038);Loss of phosphorylation at S191 (P = 0.038);Loss of phosphorylation at S191 (P = 0.038);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;