Variant rs2298278 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016169.4(SUFU):c.*391A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 400,716 control chromosomes in the GnomAD database, including 6,502 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2263 hom., cov: 33)

Exomes 𝑓: 0.15 ( 4239 hom. )

Consequence

SUFU
NM_016169.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.871

Variant links:

Genes affected

SUFU (HGNC:16466): (SUFU negative regulator of hedgehog signaling) The Hedgehog signaling pathway plays an important role in early human development. The pathway is a signaling cascade that plays a role in pattern formation and cellular proliferation during development. This gene encodes a negative regulator of the hedgehog signaling pathway. Defects in this gene are a cause of medulloblastoma. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

SUFU links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 10-102630546-A-G is Benign according to our data. Variant chr10-102630546-A-G is described in ClinVar as [Benign]. Clinvar id is 298581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUFU	NM_016169.4 linkuse as main transcript	c.*391A>G		3_prime_UTR_variant	12/12	ENST00000369902.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUFU	ENST00000369902.8 linkuse as main transcript	c.*391A>G		3_prime_UTR_variant	12/12	1	NM_016169.4	P1	Q9UMX1-1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23088

AN:

152104

Hom.:

2255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.0642

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.0727

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0939

Gnomad OTH

AF:

0.163

GnomAD4 exome

AF:

0.148

AC:

36803

AN:

248492

Hom.:

4239

Cov.:

AF XY:

0.153

AC XY:

19457

AN XY:

126968

show subpopulations

Gnomad4 AFR exome

AF:

0.222

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.0681

Gnomad4 EAS exome

AF:

0.449

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.0792

Gnomad4 NFE exome

AF:

0.0892

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.152

AC:

23132

AN:

152224

Hom.:

2263

Cov.:

AF XY:

0.155

AC XY:

11509

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.218

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.0642

Gnomad4 EAS

AF:

0.414

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.0727

Gnomad4 NFE

AF:

0.0939

Gnomad4 OTH

AF:

0.166

Alfa

AF:

0.125

Hom.:

717

Bravo

AF:

0.167

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Medulloblastoma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.84

DANN

Benign

0.31

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over