Genetic Variant LANCL2:p.Thr4Asn (chr7-55366036-C-A) – 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.11C>A(p.Thr4Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000749 in 1,335,922 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T4I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

LANCL2
NM_018697.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.951

Publications

0 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=0.07127562).

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.11C>A	p.Thr4Asn	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.11C>A	p.Thr4Asn	missense	Exon 1 of 9	ENSP00000254770.2	Q9NS86
LANCL2	ENST00000952390.1		c.11C>A	p.Thr4Asn	missense	Exon 1 of 10	ENSP00000622449.1
LANCL2	ENST00000952391.1		c.11C>A	p.Thr4Asn	missense	Exon 1 of 9	ENSP00000622450.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.49e-7

AC:

AN:

1335922

Hom.:

Cov.:

AF XY:

0.00000153

AC XY:

AN XY:

654528

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27230

American (AMR)

AF:

0.00

AC:

AN:

27928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22088

East Asian (EAS)

AF:

0.00

AC:

AN:

31612

South Asian (SAS)

AF:

0.00

AC:

AN:

73636

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47976

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5408

European-Non Finnish (NFE)

AF:

9.57e-7

AC:

AN:

1045376

Other (OTH)

AF:

0.00

AC:

AN:

54668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0047

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.022

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.75

M_CAP

Benign

0.044

MetaRNN

Benign

0.071

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

PhyloP100

0.95

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.27

REVEL

Benign

0.053

Sift

Benign

0.24

Sift4G

Benign

0.57

Polyphen

0.0010

Vest4

0.094

MutPred

0.11

Loss of phosphorylation at T4 (P = 0.0884)

MVP

0.19

MPC

0.29

ClinPred

0.43

GERP RS

4.5

Varity_R

0.14

gMVP

0.42

Mutation Taster

=80/20

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over