rs10493937

chr1-100877094-T-A

Variant summary

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

The NM_001033025.3(EXTL2):c.434-230A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,806 control chromosomes in the GnomAD database, including 13,780 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13780 hom., cov: 31)
• Consequence: EXTL2 NM_001033025.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120

Genes affected

EXTL2 (HGNC:3516): (exostosin like glycosyltransferase 2) Enables alpha-1,4-N-acetylgalactosaminyltransferase activity and glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity. Involved in N-acetylglucosamine metabolic process and UDP-N-acetylgalactosamine metabolic process. Located in cytosol; endoplasmic reticulum; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXTL2	NM_001033025.3	c.434-230A>T		intron_variant		ENST00000370114.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXTL2	ENST00000370114.8	c.434-230A>T		intron_variant		1	NM_001033025.3	P1
EXTL2	ENST00000370113.7	c.434-230A>T		intron_variant		1		P1
EXTL2	ENST00000450240.2	c.458-230A>T		intron_variant		4
EXTL2	ENST00000535414.5	c.433+382A>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61943 AN: 151688 Hom.: 13787 Cov.: 31

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.410

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.408 AC: 61957 AN: 151806 Hom.: 13780 Cov.: 31 AF XY: 0.403 AC XY: 29917 AN XY: 74168

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.408

Alfa AF: 0.456 Hom.: 2081

Bravo AF: 0.392

Asia WGS AF: 0.273 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.9
Dann	Benign	0.48

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: rs10493937; hg19: chr1-101342650;