rs10493937

Variant names:

• chr1-100877094-T-A
• rs10493937
• NM_001033025.3:c.434-230A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033025.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXTL2	NM_001033025.3	MANE Select	c.434-230A>T		intron	N/A	NP_001028197.1	Q9UBQ6
	EXTL2	NM_001261441.2		c.458-230A>T		intron	N/A	NP_001248370.1
	EXTL2	NM_001439.4		c.434-230A>T		intron	N/A	NP_001430.1	Q9UBQ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXTL2	ENST00000370114.8	TSL:1 MANE Select	c.434-230A>T		intron	N/A	ENSP00000359132.3	Q9UBQ6
	EXTL2	ENST00000370113.7	TSL:1	c.434-230A>T		intron	N/A	ENSP00000359131.3	Q9UBQ6
	EXTL2	ENST00000886545.1		c.458-230A>T		intron	N/A	ENSP00000556603.1

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

African (AFR) AF: 0.242 AC: 10008 AN: 41414

American (AMR) AF: 0.410 AC: 6249 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1758 AN: 3466

East Asian (EAS) AF: 0.219 AC: 1129 AN: 5152

South Asian (SAS) AF: 0.353 AC: 1698 AN: 4816

European-Finnish (FIN) AF: 0.491 AC: 5164 AN: 10510

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.510 AC: 34617 AN: 67910

Other (OTH) AF: 0.408 AC: 859 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.48
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10493937; hg19: chr1-101342650;