rs6709245

Variant names:

• chr2-131491303-A-G
• rs6709245
• NM_001085365.2:c.319+573T>C

Variant summary

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

The NM_001085365.2(MZT2A):​c.319+573T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 287,440 control chromosomes in the GnomAD database, including 26,338 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 0.44 (17041 hom., cov: 32)
  • Exomes 𝑓: 0.34 (9297 hom.)
• Consequence: MZT2A NM_001085365.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630
• Publications: 9 publications found

Genes affected

MZT2A (HGNC:33187): (mitotic spindle organizing protein 2A) Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MIR4784 (HGNC:41580): (microRNA 4784) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MZT2A	NM_001085365.2	c.319+573T>C		intron_variant	Intron 2 of 2	ENST00000309451.7	NP_001078834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MZT2A	ENST00000309451.7	c.319+573T>C		intron_variant	Intron 2 of 2	1	NM_001085365.2	ENSP00000311500.6

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66075 AN: 151600 Hom.: 16987 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.447

GnomAD4 exome AF: 0.339 AC: 46008 AN: 135724 Hom.: 9297 Cov.: 0 AF XY: 0.344 AC XY: 24610 AN XY: 71618

African (AFR) AF: 0.651 AC: 2512 AN: 3858

American (AMR) AF: 0.592 AC: 3397 AN: 5734

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1329 AN: 3376

East Asian (EAS) AF: 0.755 AC: 4268 AN: 5656

South Asian (SAS) AF: 0.387 AC: 8471 AN: 21874

European-Finnish (FIN) AF: 0.315 AC: 2155 AN: 6838

Middle Eastern (MID) AF: 0.361 AC: 259 AN: 718

European-Non Finnish (NFE) AF: 0.264 AC: 21261 AN: 80558

Other (OTH) AF: 0.331 AC: 2356 AN: 7112

GnomAD4 genome AF: 0.436 AC: 66197 AN: 151716 Hom.: 17041 Cov.: 32 AF XY: 0.444 AC XY: 32911 AN XY: 74128

African (AFR) AF: 0.659 AC: 27267 AN: 41406

American (AMR) AF: 0.552 AC: 8426 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1328 AN: 3462

East Asian (EAS) AF: 0.766 AC: 3946 AN: 5150

South Asian (SAS) AF: 0.412 AC: 1969 AN: 4782

European-Finnish (FIN) AF: 0.319 AC: 3357 AN: 10538

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18578 AN: 67808

Other (OTH) AF: 0.453 AC: 956 AN: 2110

Alfa AF: 0.322 Hom.: 26759

Bravo AF: 0.467

Asia WGS AF: 0.583 AC: 2025 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.7
DANN	Benign	0.42
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs6709245; hg19: chr2-132248876;