rs2298278

Variant names:

• chr10-102630546-A-G
• rs2298278
• NM_016169.4:c.*391A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-102630546-A-G
• chr10-102630546-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.871
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• medulloblastoma

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• nevoid basal cell carcinoma syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Illumina, Genomics England PanelApp
• basal cell nevus syndrome 2

  Inheritance: AD Classification: STRONG Submitted by: G2P
• ocular motor apraxia, Cogan type

  Inheritance: AD Classification: STRONG Submitted by: Franklin by Genoox
• Joubert syndrome 32

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Joubert syndrome

  Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
• apraxia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• ciliopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SUFU	NM_016169.4	c.*391A>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000369902.8	NP_057253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8	c.*391A>G		3_prime_UTR_variant	Exon 12 of 12	1	NM_016169.4	ENSP00000358918.4

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23088 AN: 152104 Hom.: 2255 Cov.: 33

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.: 0 AF XY: 0.153 AC XY: 19457 AN XY: 126968

African (AFR) AF: 0.222 AC: 2020 AN: 9112

American (AMR) AF: 0.232 AC: 2639 AN: 11366

Ashkenazi Jewish (ASJ) AF: 0.0681 AC: 625 AN: 9182

East Asian (EAS) AF: 0.449 AC: 8646 AN: 19246

South Asian (SAS) AF: 0.234 AC: 7423 AN: 31660

European-Finnish (FIN) AF: 0.0792 AC: 592 AN: 7476

Middle Eastern (MID) AF: 0.119 AC: 129 AN: 1082

European-Non Finnish (NFE) AF: 0.0892 AC: 12856 AN: 144188

Other (OTH) AF: 0.123 AC: 1873 AN: 15180

GnomAD4 genome AF: 0.152 AC: 23132 AN: 152224 Hom.: 2263 Cov.: 33 AF XY: 0.155 AC XY: 11509 AN XY: 74428

African (AFR) AF: 0.218 AC: 9072 AN: 41534

American (AMR) AF: 0.195 AC: 2984 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0642 AC: 223 AN: 3472

East Asian (EAS) AF: 0.414 AC: 2136 AN: 5154

South Asian (SAS) AF: 0.222 AC: 1074 AN: 4828

European-Finnish (FIN) AF: 0.0727 AC: 772 AN: 10614

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0939 AC: 6385 AN: 68006

Other (OTH) AF: 0.166 AC: 351 AN: 2114

Alfa AF: 0.125 Hom.: 997

Bravo AF: 0.167

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Medulloblastoma Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.87
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: rs2298278; hg19: chr10-104390303;