chr7-55398486-C-G

Variant names:

• chr7-55398486-C-G
• NM_018697.4:c.386C>G

Variant summary

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

The NM_018697.4(LANCL2):​c.386C>G​(p.Ser129Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• 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.386C>G	p.Ser129Cys	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.386C>G	p.Ser129Cys	missense	Exon 3 of 9	ENSP00000254770.2	Q9NS86
	LANCL2	ENST00000952390.1		c.386C>G	p.Ser129Cys	missense	Exon 3 of 10	ENSP00000622449.1
	LANCL2	ENST00000952391.1		c.386C>G	p.Ser129Cys	missense	Exon 3 of 9	ENSP00000622450.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60396

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	Benign	0.12
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.0079
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0063	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.89	L
PhyloP100		7.3
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.18
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.15	T
Polyphen		0.0090	B
Vest4		0.67
MutPred		0.70		Gain of catalytic residue at L130 (P = 0.0583)
MVP		0.18
MPC		0.89
ClinPred		0.80	D
GERP RS		5.5
Varity_R		0.43
gMVP		0.42
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr7-55466179;