rs2842977

Variant names:

• chr6-159742891-A-G
• rs2842977
• NM_001270531.2:c.145+745A>G

Variant summary

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

The NM_001270531.2(WTAP):​c.145+745A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,246 control chromosomes in the GnomAD database, including 18,471 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 0.47 (18471 hom., cov: 28)
• Consequence: WTAP NM_001270531.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 5 publications found

Genes affected

WTAP (HGNC:16846): (WT1 associated protein) The Wilms tumor suppressor gene WT1 appears to play a role in both transcriptional and posttranscriptional regulation of certain cellular genes. This gene encodes a WT1-associating protein, which is a ubiquitously expressed nuclear protein. Like WT1 protein, this protein is localized throughout the nucleoplasm as well as in speckles and partially colocalizes with splicing factors. Alternative splicing of this gene results in several transcript variants encoding three different isoforms. [provided by RefSeq, Jul 2012]

SOD2 (HGNC:11180): (superoxide dismutase 2) This gene is a member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial protein that forms a homotetramer and binds one manganese ion per subunit. This protein binds to the superoxide byproducts of oxidative phosphorylation and converts them to hydrogen peroxide and diatomic oxygen. Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC), premature aging, sporadic motor neuron disease, and cancer. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 1. [provided by RefSeq, Apr 2016]

SOD2 Gene-Disease associations (from GenCC):

• cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WTAP	NM_001270531.2	c.145+745A>G		intron_variant	Intron 4 of 7	ENST00000621533.5	NP_001257460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WTAP	ENST00000621533.5	c.145+745A>G		intron_variant	Intron 4 of 7	2	NM_001270531.2	ENSP00000479438.1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70495 AN: 151132 Hom.: 18466 Cov.: 28

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.466 AC: 70492 AN: 151246 Hom.: 18471 Cov.: 28 AF XY: 0.464 AC XY: 34277 AN XY: 73832

African (AFR) AF: 0.237 AC: 9782 AN: 41270

American (AMR) AF: 0.567 AC: 8619 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2070 AN: 3466

East Asian (EAS) AF: 0.182 AC: 932 AN: 5134

South Asian (SAS) AF: 0.501 AC: 2407 AN: 4802

European-Finnish (FIN) AF: 0.558 AC: 5749 AN: 10310

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39313 AN: 67766

Other (OTH) AF: 0.478 AC: 1003 AN: 2098

Alfa AF: 0.513 Hom.: 2807

Bravo AF: 0.457

Asia WGS AF: 0.345 AC: 1195 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.7
DANN	Benign	0.66
PhyloP100		0.024
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: rs2842977; hg19: chr6-160163923;