Genetic Variant NM_018697.4:c.122C>G (chr7-55366147-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018697.4(LANCL2):c.122C>G(p.Ser41Cys) 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. 15/22 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. S41F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LANCL2
NM_018697.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.30

Publications

1 publications found

Variant links:

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]

LANCL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12611896).

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.122C>G	p.Ser41Cys	missense	Exon 1 of 9	NP_061167.1	Q9NS86

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LANCL2	ENST00000254770.3	TSL:1 MANE Select	c.122C>G	p.Ser41Cys	missense	Exon 1 of 9	ENSP00000254770.2	Q9NS86
LANCL2	ENST00000952390.1		c.122C>G	p.Ser41Cys	missense	Exon 1 of 10	ENSP00000622449.1
LANCL2	ENST00000952391.1		c.122C>G	p.Ser41Cys	missense	Exon 1 of 9	ENSP00000622450.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1398782

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689762

African (AFR)

AF:

0.00

AC:

AN:

30870

American (AMR)

AF:

0.00

AC:

AN:

36960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24734

East Asian (EAS)

AF:

0.00

AC:

AN:

36068

South Asian (SAS)

AF:

0.00

AC:

AN:

79198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49252

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5596

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078356

Other (OTH)

AF:

0.00

AC:

AN:

57748

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.020

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.23

M_CAP

Benign

0.0066

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

3.3

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.80

REVEL

Benign

0.048

Sift

Benign

0.075

Sift4G

Uncertain

0.025

Polyphen

0.070

Vest4

0.096

MutPred

0.44

Loss of glycosylation at S41 (P = 0.0011)

MVP

0.21

MPC

0.29

ClinPred

0.22

GERP RS

3.5

Varity_R

0.091

gMVP

0.28

Mutation Taster

=77/23

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over