rs117755165

Positions:

• chr11-44244388-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_207122.2(EXT2):​c.*101G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00444 in 1,352,236 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (24 hom.)
• Consequence: EXT2 NM_207122.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.627

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=-0.78).
• BP6: Variant 11-44244388-G-C is Benign according to our data. Variant chr11-44244388-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 304597.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00332 (505/152314) while in subpopulation NFE AF= 0.00506 (344/68026). AF 95% confidence interval is 0.00462. There are 1 homozygotes in gnomad4. There are 236 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 505 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXT2	NM_207122.2	c.*101G>C		3_prime_UTR_variant	14/14	ENST00000533608.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXT2	ENST00000533608.7	c.*101G>C		3_prime_UTR_variant	14/14	1	NM_207122.2	P1

Frequencies

GnomAD3 genomes AF: 0.00332 AC: 506 AN: 152196 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00477

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00507

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.00458 AC: 5499 AN: 1199922 Hom.: 24 Cov.: 16 AF XY: 0.00449 AC XY: 2726 AN XY: 607476

Gnomad4 AFR exome AF: 0.00138

Gnomad4 AMR exome AF: 0.00376

Gnomad4 ASJ exome AF: 0.00481

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000854

Gnomad4 FIN exome AF: 0.000795

Gnomad4 NFE exome AF: 0.00546

Gnomad4 OTH exome AF: 0.00437

GnomAD4 genome AF: 0.00332 AC: 505 AN: 152314 Hom.: 1 Cov.: 32 AF XY: 0.00317 AC XY: 236 AN XY: 74494

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00506

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00318 Hom.: 0

Bravo AF: 0.00345

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Exostoses, multiple, type 2 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.6
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs117755165; hg19: chr11-44265938;