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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nevoid basal cell carcinoma syndrome

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

  Inheritance: AD Classification: STRONG Submitted by: G2P
• neurodevelopmental disorder

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

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

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016169.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUFU	NM_016169.4	MANE Select	c.*391A>G		3_prime_UTR	Exon 12 of 12	NP_057253.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUFU	ENST00000369902.8	TSL:1 MANE Select	c.*391A>G		3_prime_UTR	Exon 12 of 12	ENSP00000358918.4	Q9UMX1-1
	SUFU	ENST00000929518.1		c.*391A>G		3_prime_UTR	Exon 13 of 13	ENSP00000599577.1
	SUFU	ENST00000893176.1		c.*391A>G		3_prime_UTR	Exon 13 of 13	ENSP00000563235.1

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Medulloblastoma (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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;