NM_018697.4:c.391G>T

Variant names:

• chr7-55398491-G-T
• NM_018697.4:c.391G>T

Variant summary

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

The NM_018697.4(LANCL2):​c.391G>T​(p.Asp131Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LANCL2 NM_018697.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.27
• Publications: 0 publications found

Genes affected

LANCL2 (HGNC:6509): (LanC like glutathione S-transferase 2) Enables phosphatidylinositol-3-phosphate binding activity; phosphatidylinositol-4-phosphate binding activity; and phosphatidylinositol-5-phosphate binding activity. Involved in negative regulation of transcription, DNA-templated and positive regulation of abscisic acid-activated signaling pathway. Located in several cellular components, including cortical actin cytoskeleton; cytosol; and nucleoplasm. [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_018697.4. 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
	LANCL2	NM_018697.4	MANE Select	c.391G>T	p.Asp131Tyr	missense	Exon 3 of 9	NP_061167.1	Q9NS86

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LANCL2	ENST00000254770.3	TSL:1 MANE Select	c.391G>T	p.Asp131Tyr	missense	Exon 3 of 9	ENSP00000254770.2	Q9NS86
	LANCL2	ENST00000952390.1		c.391G>T	p.Asp131Tyr	missense	Exon 3 of 10	ENSP00000622449.1
	LANCL2	ENST00000952391.1		c.391G>T	p.Asp131Tyr	missense	Exon 3 of 9	ENSP00000622450.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.3
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.010	D
Polyphen		0.97	D
Vest4		0.80
MutPred		0.52		Gain of MoRF binding (P = 0.0727)
MVP		0.37
MPC		1.0
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.73
gMVP		0.61
Mutation Taster		=10/90	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

Other links and lift over

hg19: chr7-55466184;