11-44095874-G-A

Position:

• chr11-44095874-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_207122.2(EXT2):​c.-31+22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 201,212 control chromosomes in the GnomAD database, including 29,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (21544 hom., cov: 34)
  • Exomes 𝑓: 0.58 (8415 hom.)
• Consequence: EXT2 NM_207122.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.134

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=-0.79).
• BP6: Variant 11-44095874-G-A is Benign according to our data. Variant chr11-44095874-G-A is described in ClinVar as [Benign]. Clinvar id is 1248779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-44095874-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXT2	NM_207122.2	c.-31+22G>A		intron_variant		ENST00000533608.7	NP_997005.1
EXT2	NM_001178083.3	c.-31+22G>A		intron_variant			NP_001171554.1
EXT2	NM_001389630.1	c.-70+22G>A		intron_variant			NP_001376559.1
EXT2	XM_047426529.1	c.-183+22G>A		intron_variant			XP_047282485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXT2	ENST00000533608.7	c.-31+22G>A		intron_variant		1	NM_207122.2	ENSP00000431173	P1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76774 AN: 151946 Hom.: 21528 Cov.: 34

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.529

GnomAD4 exome AF: 0.581 AC: 28577 AN: 49158 Hom.: 8415 Cov.: 0 AF XY: 0.578 AC XY: 14553 AN XY: 25160

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.703

Gnomad4 ASJ exome AF: 0.549

Gnomad4 EAS exome AF: 0.703

Gnomad4 SAS exome AF: 0.556

Gnomad4 FIN exome AF: 0.653

Gnomad4 NFE exome AF: 0.580

Gnomad4 OTH exome AF: 0.584

GnomAD4 genome AF: 0.505 AC: 76840 AN: 152054 Hom.: 21544 Cov.: 34 AF XY: 0.514 AC XY: 38185 AN XY: 74324

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.534

Alfa AF: 0.399 Hom.: 1198

Bravo AF: 0.497

Asia WGS AF: 0.622 AC: 2147 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.79
CADD	Benign	7.2
DANN	Benign	0.95
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: rs12365753; hg19: chr11-44117424;