rs143595300

chr11-44171593-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_207122.2(EXT2):c.1174-18G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 1,614,062 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (17 hom., cov: 32)
  • Exomes 𝑓: 0.017 (234 hom.)
• Consequence: EXT2 NM_207122.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.15

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-44171593-G-T is Benign according to our data. Variant chr11-44171593-G-T is described in ClinVar as [Benign]. Clinvar id is 263286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-44171593-G-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0111 (1692/152266) while in subpopulation NFE AF= 0.019 (1292/68018). AF 95% confidence interval is 0.0181. There are 17 homozygotes in gnomad4. There are 785 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1693 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXT2	NM_207122.2	c.1174-18G>T		intron_variant		ENST00000533608.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXT2	ENST00000533608.7	c.1174-18G>T		intron_variant		1	NM_207122.2	P1

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1693 AN: 152148 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.00319

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.00701

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00820

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0190

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.0101 AC: 2546 AN: 251464 Hom.: 17 AF XY: 0.0101 AC XY: 1369 AN XY: 135910

Gnomad AFR exome AF: 0.00369

Gnomad AMR exome AF: 0.00408

Gnomad ASJ exome AF: 0.00357

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00186

Gnomad FIN exome AF: 0.00915

Gnomad NFE exome AF: 0.0175

Gnomad OTH exome AF: 0.00961

GnomAD4 exome AF: 0.0168 AC: 24511 AN: 1461796 Hom.: 234 Cov.: 31 AF XY: 0.0162 AC XY: 11808 AN XY: 727194

Gnomad4 AFR exome AF: 0.00317

Gnomad4 AMR exome AF: 0.00405

Gnomad4 ASJ exome AF: 0.00509

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00214

Gnomad4 FIN exome AF: 0.00955

Gnomad4 NFE exome AF: 0.0203

Gnomad4 OTH exome AF: 0.0138

GnomAD4 genome AF: 0.0111 AC: 1692 AN: 152266 Hom.: 17 Cov.: 32 AF XY: 0.0105 AC XY: 785 AN XY: 74440

Gnomad4 AFR AF: 0.00315

Gnomad4 AMR AF: 0.00700

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00820

Gnomad4 NFE AF: 0.0190

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.0123 Hom.: 2

Bravo AF: 0.0108

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Exostoses, multiple, type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Exostoses, multiple, type 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.18
Dann	Benign	0.67

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: rs143595300; hg19: chr11-44193143;