chr11-44095894-A-G

Position:

• chr11-44095894-A-G

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+42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 235,268 control chromosomes in the GnomAD database, including 62,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (39621 hom., cov: 35)
  • Exomes 𝑓: 0.74 (22636 hom.)
• Consequence: EXT2 NM_207122.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.400

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=-0.87).
• BP6: Variant 11-44095894-A-G is Benign according to our data. Variant chr11-44095894-A-G is described in ClinVar as [Benign]. Clinvar id is 1236902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-44095894-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXT2	NM_207122.2	c.-31+42A>G		intron_variant		ENST00000533608.7	NP_997005.1
EXT2	NM_001178083.3	c.-31+42A>G		intron_variant			NP_001171554.1
EXT2	NM_001389630.1	c.-70+42A>G		intron_variant			NP_001376559.1
EXT2	XM_047426529.1	c.-183+42A>G		intron_variant			XP_047282485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXT2	ENST00000533608.7	c.-31+42A>G		intron_variant		1	NM_207122.2	ENSP00000431173	P1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109332 AN: 151922 Hom.: 39572 Cov.: 35

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.717

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.723

GnomAD4 exome AF: 0.735 AC: 61183 AN: 83238 Hom.: 22636 Cov.: 0 AF XY: 0.735 AC XY: 32522 AN XY: 44224

Gnomad4 AFR exome AF: 0.676

Gnomad4 AMR exome AF: 0.842

Gnomad4 ASJ exome AF: 0.691

Gnomad4 EAS exome AF: 0.886

Gnomad4 SAS exome AF: 0.753

Gnomad4 FIN exome AF: 0.780

Gnomad4 NFE exome AF: 0.722

Gnomad4 OTH exome AF: 0.721

GnomAD4 genome AF: 0.720 AC: 109437 AN: 152030 Hom.: 39621 Cov.: 35 AF XY: 0.726 AC XY: 53974 AN XY: 74320

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.804

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.710

Gnomad4 OTH AF: 0.726

Alfa AF: 0.715 Hom.: 4830

Bravo AF: 0.720

Asia WGS AF: 0.797 AC: 2751 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	-0.87
CADD	Benign	11
DANN	Benign	0.43

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: rs12362775; hg19: chr11-44117444;