rs10838532

Positions:

• chr11-45925913-G-C

Variant summary

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

The ENST00000401752.6(LARGE2):​c.770-126G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 778,040 control chromosomes in the GnomAD database, including 19,834 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 0.18 (3024 hom., cov: 33)
  • Exomes 𝑓: 0.23 (16810 hom.)
• Consequence: LARGE2 ENST00000401752.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615

Genes affected

LARGE2 (HGNC:16522): (LARGE xylosyl- and glucuronyltransferase 2) Predicted to enable dystroglycan binding activity; glucuronosyltransferase activity; and xylosyltransferase activity. Involved in protein O-linked mannosylation. Predicted to be located in intracellular membrane-bounded organelle. Predicted to be active in Golgi apparatus. [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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARGE2	NM_001300721.2	c.770-126G>C		intron_variant		ENST00000401752.6	NP_001287650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARGE2	ENST00000401752.6	c.770-126G>C		intron_variant		1	NM_001300721.2	ENSP00000385235	P2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27547 AN: 152036 Hom.: 3024 Cov.: 33

Gnomad AFR AF: 0.0671

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.225 AC: 141048 AN: 625886 Hom.: 16810 AF XY: 0.224 AC XY: 71678 AN XY: 320578

Gnomad4 AFR exome AF: 0.0614

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.181 AC: 27563 AN: 152154 Hom.: 3024 Cov.: 33 AF XY: 0.180 AC XY: 13375 AN XY: 74358

Gnomad4 AFR AF: 0.0674

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.169

Alfa AF: 0.209 Hom.: 488

Bravo AF: 0.167

Asia WGS AF: 0.175 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.70

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: rs10838532; hg19: chr11-45947464;