6-159733067-G-C

Variant names:

• chr6-159733067-G-C
• rs2758313
• NM_001270531.2:c.-8-3191G>C

Variant summary

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

The NM_001270531.2(WTAP):​c.-8-3191G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,004 control chromosomes in the GnomAD database, including 47,179 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 0.79 (47179 hom., cov: 31)
• Consequence: WTAP NM_001270531.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385
• Publications: 10 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WTAP	NM_001270531.2	c.-8-3191G>C		intron_variant	Intron 1 of 7	ENST00000621533.5	NP_001257460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WTAP	ENST00000621533.5	c.-8-3191G>C		intron_variant	Intron 1 of 7	2	NM_001270531.2	ENSP00000479438.1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119369 AN: 151886 Hom.: 47146 Cov.: 31

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.797

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

GnomAD4 genome AF: 0.786 AC: 119455 AN: 152004 Hom.: 47179 Cov.: 31 AF XY: 0.788 AC XY: 58555 AN XY: 74288

African (AFR) AF: 0.773 AC: 32006 AN: 41422

American (AMR) AF: 0.838 AC: 12804 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2592 AN: 3472

East Asian (EAS) AF: 0.585 AC: 3021 AN: 5168

South Asian (SAS) AF: 0.847 AC: 4081 AN: 4816

European-Finnish (FIN) AF: 0.834 AC: 8795 AN: 10550

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.790 AC: 53678 AN: 67984

Other (OTH) AF: 0.790 AC: 1669 AN: 2112

Alfa AF: 0.741 Hom.: 2262

Bravo AF: 0.782

Asia WGS AF: 0.708 AC: 2459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.45
PhyloP100		-0.39
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: rs2758313; hg19: chr6-160154099;