7-55398491-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LANCL2	NM_018697.4	c.391G>T	p.Asp131Tyr	missense_variant	Exon 3 of 9	ENST00000254770.3	NP_061167.1
LANCL2	XM_047420614.1	c.130G>T	p.Asp44Tyr	missense_variant	Exon 4 of 10		XP_047276570.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LANCL2	ENST00000254770.3	c.391G>T	p.Asp131Tyr	missense_variant	Exon 3 of 9	1	NM_018697.4	ENSP00000254770.2
LANCL2	ENST00000452107.6	n.*371G>T		non_coding_transcript_exon_variant	Exon 4 of 10	5		ENSP00000387598.2
LANCL2	ENST00000486376.1	n.399G>T		non_coding_transcript_exon_variant	Exon 3 of 4	5
LANCL2	ENST00000452107.6	n.*371G>T		3_prime_UTR_variant	Exon 4 of 10	5		ENSP00000387598.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 20, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.391G>T (p.D131Y) alteration is located in exon 3 (coding exon 3) of the LANCL2 gene. This alteration results from a G to T substitution at nucleotide position 391, causing the aspartic acid (D) at amino acid position 131 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-55466184;