LARGE2 p.Phe356Leu

Variant names:

• chr11-45926501-C-A
• NM_001300721.2:c.1068C>A
• LARGE2 p.Phe356Leu

Your query was ambiguous. Multiple possible variants found:

• chr11-45926501-C-A
• chr11-45926501-C-G
• chr11-45926499-T-C
• chr11-45926499-TTC-CTT
• chr11-45926499-TTC-CTA
• chr11-45926499-TTC-CTG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001300721.2(LARGE2):​c.1068C>A​(p.Phe356Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LARGE2 NM_001300721.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.71
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300721.2. 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
	LARGE2	NM_001300721.2	MANE Select	c.1068C>A	p.Phe356Leu	missense	Exon 9 of 14	NP_001287650.1	Q8N3Y3
	LARGE2	NM_152312.5		c.1068C>A	p.Phe356Leu	missense	Exon 9 of 14	NP_689525.3
	LARGE2	NM_001300722.2		c.975C>A	p.Phe325Leu	missense	Exon 10 of 15	NP_001287651.1	E9PIZ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARGE2	ENST00000401752.6	TSL:1 MANE Select	c.1068C>A	p.Phe356Leu	missense	Exon 9 of 14	ENSP00000385235.1	Q8N3Y3
	LARGE2	ENST00000325468.9	TSL:1	c.1068C>A	p.Phe356Leu	missense	Exon 8 of 13	ENSP00000324570.5	Q8N3Y3
	LARGE2	ENST00000530437.5	TSL:1	n.139C>A		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.7
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.27
Sift	Benign	0.23	T
Sift4G	Benign	0.10	T
PromoterAI		0.043	Neutral
Varity_R		0.56
gMVP		0.83
Mutation Taster		=23/77	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-45948052;