Variant 11-44095822-C-G 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_207122.2(EXT2):c.-61C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 166,824 control chromosomes in the GnomAD database, including 329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 284 hom., cov: 33)

Exomes 𝑓: 0.064 ( 45 hom. )

Consequence

EXT2
NM_207122.2 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.43

Variant links:

Genes affected

EXT2 (HGNC:3513): (exostosin glycosyltransferase 2) This gene encodes one of two glycosyltransferases involved in the chain elongation step of heparan sulfate biosynthesis. Mutations in this gene cause the type II form of multiple exostoses. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

EXT2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 11-44095822-C-G is Benign according to our data. Variant chr11-44095822-C-G is described in ClinVar as [Benign]. Clinvar id is 304568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
EXT2	NM_207122.2 linkuse as main transcript	c.-61C>G	5_prime_UTR_variant	1/14	ENST00000533608.7
EXT2	NM_001178083.3 linkuse as main transcript	c.-61C>G	5_prime_UTR_variant	1/15
EXT2	NM_001389630.1 linkuse as main transcript	c.-100C>G	5_prime_UTR_variant	1/15
EXT2	XM_047426529.1 linkuse as main transcript	c.-213C>G	5_prime_UTR_variant	1/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXT2	ENST00000533608.7 linkuse as main transcript	c.-61C>G		5_prime_UTR_variant	1/14	1	NM_207122.2	P1	Q93063-1

Frequencies

GnomAD3 genomes

AF:

0.0491

AC:

7471

AN:

152136

Hom.:

284

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0375

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.000776

Gnomad SAS

AF:

0.0186

Gnomad FIN

AF:

0.0663

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0784

Gnomad OTH

AF:

0.0440

GnomAD4 exome

AF:

0.0639

AC:

931

AN:

14580

Hom.:

Cov.:

AF XY:

0.0609

AC XY:

446

AN XY:

7320

show subpopulations

Gnomad4 AFR exome

AF:

0.0266

Gnomad4 AMR exome

AF:

0.0515

Gnomad4 ASJ exome

AF:

0.0213

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0192

Gnomad4 FIN exome

AF:

0.0675

Gnomad4 NFE exome

AF:

0.0733

Gnomad4 OTH exome

AF:

0.0582

GnomAD4 genome

AF:

0.0491

AC:

7472

AN:

152244

Hom.:

284

Cov.:

AF XY:

0.0474

AC XY:

3526

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0138

Gnomad4 AMR

AF:

0.0375

Gnomad4 ASJ

AF:

0.0228

Gnomad4 EAS

AF:

0.000778

Gnomad4 SAS

AF:

0.0186

Gnomad4 FIN

AF:

0.0663

Gnomad4 NFE

AF:

0.0784

Gnomad4 OTH

AF:

0.0435

Alfa

AF:

0.0623

Hom.:

Bravo

AF:

0.0456

Asia WGS

AF:

0.00812

AC:

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Exostoses, multiple, type 2

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.89

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