rs77554103

chr11-44244343-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207122.2(EXT2):c.*56G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00545 in 1,592,502 control chromosomes in the GnomAD database, including 258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (7 hom., cov: 31)
  • Exomes 𝑓: 0.0055 (251 hom.)
• Consequence: EXT2 NM_207122.2 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.385

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXT2	NM_207122.2	c.*56G>A		3_prime_UTR_variant	14/14	ENST00000533608.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXT2	ENST00000533608.7	c.*56G>A		3_prime_UTR_variant	14/14	1	NM_207122.2	P1

Frequencies

GnomAD3 genomes AF: 0.00495 AC: 753 AN: 152190 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.0432

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00184

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.00550 AC: 7928 AN: 1440194 Hom.: 251 Cov.: 26 AF XY: 0.00552 AC XY: 3958 AN XY: 717634

Gnomad4 AFR exome AF: 0.000575

Gnomad4 AMR exome AF: 0.0407

Gnomad4 ASJ exome AF: 0.00135

Gnomad4 EAS exome AF: 0.0797

Gnomad4 SAS exome AF: 0.0114

Gnomad4 FIN exome AF: 0.00160

Gnomad4 NFE exome AF: 0.00134

Gnomad4 OTH exome AF: 0.00535

GnomAD4 genome AF: 0.00494 AC: 753 AN: 152308 Hom.: 7 Cov.: 31 AF XY: 0.00528 AC XY: 393 AN XY: 74466

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.0168

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.0431

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00184

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00401 Hom.: 2

Bravo AF: 0.00650

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Exostoses, multiple, type 2 Benign:2

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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Nov 08, 2022	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	6.3
Dann	Benign	0.48
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: rs77554103; hg19: chr11-44265893; COSMIC: COSV59151511; COSMIC: COSV59151511;