NM_014943.5:c.-282-2379A>G

Variant names:

• chr8-122861098-A-G
• rs11779768
• NM_014943.5:c.-282-2379A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014943.5(ZHX2):​c.-282-2379A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 149,950 control chromosomes in the GnomAD database, including 7,132 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 0.30 (7132 hom., cov: 28)
• Consequence: ZHX2 NM_014943.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• Publications: 4 publications found

Genes affected

ZHX2 (HGNC:18513): (zinc fingers and homeoboxes 2) The members of the zinc fingers and homeoboxes gene family are nuclear homodimeric transcriptional repressors that interact with the A subunit of nuclear factor-Y (NF-YA) and contain two C2H2-type zinc fingers and five homeobox DNA-binding domains. This gene encodes member 2 of this gene family. In addition to forming homodimers, this protein heterodimerizes with member 1 of the zinc fingers and homeoboxes family. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014943.5. 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
	ZHX2	NM_014943.5	MANE Select	c.-282-2379A>G		intron	N/A	NP_055758.1
	ZHX2	NM_001362797.2		c.-437-2379A>G		intron	N/A	NP_001349726.1
	ZHX2	NM_001412796.1		c.-420-2379A>G		intron	N/A	NP_001399725.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZHX2	ENST00000314393.6	TSL:1 MANE Select	c.-282-2379A>G		intron	N/A	ENSP00000314709.4
	ZHX2	ENST00000892386.1		c.-437-2379A>G		intron	N/A	ENSP00000562445.1
	ZHX2	ENST00000892387.1		c.-344-2379A>G		intron	N/A	ENSP00000562446.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 44697 AN: 149844 Hom.: 7123 Cov.: 28

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.297

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.298 AC: 44729 AN: 149950 Hom.: 7132 Cov.: 28 AF XY: 0.302 AC XY: 22017 AN XY: 72870

African (AFR) AF: 0.220 AC: 8990 AN: 40832

American (AMR) AF: 0.237 AC: 3566 AN: 15050

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 883 AN: 3468

East Asian (EAS) AF: 0.366 AC: 1830 AN: 5006

South Asian (SAS) AF: 0.366 AC: 1740 AN: 4752

European-Finnish (FIN) AF: 0.429 AC: 4187 AN: 9754

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22501 AN: 67800

Other (OTH) AF: 0.300 AC: 626 AN: 2086

Alfa AF: 0.314 Hom.: 3504

Bravo AF: 0.280

Asia WGS AF: 0.338 AC: 1176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.1
DANN	Benign	0.81
PhyloP100		0.29
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: rs11779768; hg19: chr8-123873337;