11-44107536-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_207122.2(EXT2):c.-30-147A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 730,360 control chromosomes in the GnomAD database, including 28,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (5056 hom., cov: 32)
  • Exomes 𝑓: 0.28 (23204 hom.)
• Consequence: EXT2 NM_207122.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.571

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 11-44107536-A-T is Benign according to our data. Variant chr11-44107536-A-T is described in ClinVar as [Benign]. Clinvar id is 1289926.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXT2	NM_207122.2	c.-30-147A>T		intron_variant		ENST00000533608.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXT2	ENST00000533608.7	c.-30-147A>T		intron_variant		1	NM_207122.2	P1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37192 AN: 151888 Hom.: 5049 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.276 AC: 159792 AN: 578354 Hom.: 23204 AF XY: 0.271 AC XY: 81037 AN XY: 298758

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.321

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.288

Gnomad4 OTH exome AF: 0.270

GnomAD4 genome AF: 0.245 AC: 37232 AN: 152006 Hom.: 5056 Cov.: 32 AF XY: 0.247 AC XY: 18316 AN XY: 74282

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.248

Alfa AF: 0.272 Hom.: 768

Bravo AF: 0.233

Asia WGS AF: 0.206 AC: 717 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.0
Dann	Benign	0.46

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

Other links and lift over

dbSNP: rs11037864; hg19: chr11-44129086;