19-56782026-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001387356.1(ZIM2):​c.666T>C​(p.Ser222Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 1,613,742 control chromosomes in the GnomAD database, including 500,021 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (45161 hom., cov: 32)
  • Exomes 𝑓: 0.79 (454860 hom.)
• Consequence: ZIM2 NM_001387356.1 synonymous
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-2.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387356.1. 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
	ZIM2	NM_001387356.1	MANE Select	c.666T>C	p.Ser222Ser	synonymous	Exon 11 of 13	NP_001374285.1
	ZIM2	NM_001369773.1		c.666T>C	p.Ser222Ser	synonymous	Exon 10 of 12	NP_001356702.1
	ZIM2	NM_001369774.1		c.666T>C	p.Ser222Ser	synonymous	Exon 10 of 12	NP_001356703.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZIM2	ENST00000629319.3	TSL:5 MANE Select	c.666T>C	p.Ser222Ser	synonymous	Exon 11 of 13	ENSP00000486502.2
	ZIM2	ENST00000593711.6	TSL:1	c.573T>C	p.Ser191Ser	synonymous	Exon 9 of 11	ENSP00000472306.1
	ZIM2	ENST00000601070.5	TSL:1	c.573T>C	p.Ser191Ser	synonymous	Exon 9 of 11	ENSP00000470326.1

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116844 AN: 151964 Hom.: 45122 Cov.: 32

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.773

GnomAD2 exomes AF: 0.793 AC: 199278 AN: 251314 AF XY: 0.796

Gnomad AFR exome AF: 0.713

Gnomad AMR exome AF: 0.858

Gnomad ASJ exome AF: 0.794

Gnomad EAS exome AF: 0.663

Gnomad FIN exome AF: 0.779

Gnomad NFE exome AF: 0.793

Gnomad OTH exome AF: 0.782

GnomAD4 exome AF: 0.788 AC: 1151656 AN: 1461660 Hom.: 454860 Cov.: 75 AF XY: 0.790 AC XY: 574113 AN XY: 727132

African (AFR) AF: 0.715 AC: 23918 AN: 33458

American (AMR) AF: 0.849 AC: 37983 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 20625 AN: 26126

East Asian (EAS) AF: 0.642 AC: 25466 AN: 39696

South Asian (SAS) AF: 0.849 AC: 73249 AN: 86242

European-Finnish (FIN) AF: 0.779 AC: 41599 AN: 53412

Middle Eastern (MID) AF: 0.768 AC: 4431 AN: 5766

European-Non Finnish (NFE) AF: 0.789 AC: 877017 AN: 1111860

Other (OTH) AF: 0.784 AC: 47368 AN: 60384

GnomAD4 genome AF: 0.769 AC: 116947 AN: 152082 Hom.: 45161 Cov.: 32 AF XY: 0.771 AC XY: 57354 AN XY: 74362

African (AFR) AF: 0.719 AC: 29806 AN: 41466

American (AMR) AF: 0.813 AC: 12433 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2761 AN: 3472

East Asian (EAS) AF: 0.665 AC: 3415 AN: 5138

South Asian (SAS) AF: 0.847 AC: 4084 AN: 4820

European-Finnish (FIN) AF: 0.774 AC: 8191 AN: 10580

Middle Eastern (MID) AF: 0.753 AC: 220 AN: 292

European-Non Finnish (NFE) AF: 0.789 AC: 53675 AN: 67998

Other (OTH) AF: 0.777 AC: 1642 AN: 2114

Alfa AF: 0.783 Hom.: 73759

Bravo AF: 0.767

Asia WGS AF: 0.776 AC: 2696 AN: 3478

EpiCase AF: 0.784

EpiControl AF: 0.785

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.61
PhyloP100		-2.2
Mutation Taster		=100/0	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: rs2286751; hg19: chr19-57293394; COSMIC: COSV55634815;