rs142152518

Variant names:

• chr7-55399974-G-A
• rs142152518
• NM_018697.4:c.548G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-55399974-G-A
• chr7-55399974-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018697.4(LANCL2):​c.548G>A​(p.Arg183Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R183I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LANCL2 NM_018697.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059490353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LANCL2	NM_018697.4	c.548G>A	p.Arg183Lys	missense_variant	Exon 4 of 9	ENST00000254770.3	NP_061167.1
LANCL2	XM_047420614.1	c.287G>A	p.Arg96Lys	missense_variant	Exon 5 of 10		XP_047276570.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LANCL2	ENST00000254770.3	c.548G>A	p.Arg183Lys	missense_variant	Exon 4 of 9	1	NM_018697.4	ENSP00000254770.2
LANCL2	ENST00000452107.6	n.*528G>A		non_coding_transcript_exon_variant	Exon 5 of 10	5		ENSP00000387598.2
LANCL2	ENST00000486376.1	n.556G>A		non_coding_transcript_exon_variant	Exon 4 of 4	5
LANCL2	ENST00000452107.6	n.*528G>A		3_prime_UTR_variant	Exon 5 of 10	5		ENSP00000387598.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.38
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.35	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.070
Sift	Benign	0.95	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.16
MutPred		0.45		Gain of ubiquitination at R183 (P = 0.0247);
MVP		0.20
MPC		0.26
ClinPred		0.074	T
GERP RS		2.7
Varity_R		0.024
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs142152518; hg19: chr7-55467667;