11-44107603-A-C

Position:

• chr11-44107603-A-C

Variant summary

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

The ENST00000533608.7(EXT2):​c.-30-80A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00621 in 1,373,290 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (61 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (232 hom.)
• Consequence: EXT2 ENST00000533608.7 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0370

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=-0.9).
• BP6: Variant 11-44107603-A-C is Benign according to our data. Variant chr11-44107603-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1327344.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXT2	NM_207122.2	c.-30-80A>C		intron_variant		ENST00000533608.7	NP_997005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXT2	ENST00000533608.7	c.-30-80A>C		intron_variant		1	NM_207122.2	ENSP00000431173	P1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2279 AN: 152160 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.00512 AC: 6246 AN: 1221012 Hom.: 232 AF XY: 0.00482 AC XY: 2921 AN XY: 605714

Gnomad4 AFR exome AF: 0.0396

Gnomad4 AMR exome AF: 0.00500

Gnomad4 ASJ exome AF: 0.00870

Gnomad4 EAS exome AF: 0.0988

Gnomad4 SAS exome AF: 0.00194

Gnomad4 FIN exome AF: 0.000137

Gnomad4 NFE exome AF: 0.000525

Gnomad4 OTH exome AF: 0.00877

GnomAD4 genome AF: 0.0150 AC: 2287 AN: 152278 Hom.: 61 Cov.: 32 AF XY: 0.0150 AC XY: 1116 AN XY: 74458

Gnomad4 AFR AF: 0.0395

Gnomad4 AMR AF: 0.00647

Gnomad4 ASJ AF: 0.00806

Gnomad4 EAS AF: 0.0780

Gnomad4 SAS AF: 0.00580

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000720

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0107 Hom.: 5

Bravo AF: 0.0169

Asia WGS AF: 0.0370 AC: 127 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.62

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: rs75844681; hg19: chr11-44129153; COSMIC: COSV59154297; COSMIC: COSV59154297;