chr7-55366111-C-T

Variant names:

• chr7-55366111-C-T
• rs374989248
• NM_018697.4:c.86C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018697.4(LANCL2):​c.86C>T​(p.Pro29Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000906 in 1,545,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: LANCL2 NM_018697.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.749
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.075372845).

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.86C>T	p.Pro29Leu	missense	Exon 1 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.86C>T	p.Pro29Leu	missense	Exon 1 of 9	ENSP00000254770.2	Q9NS86
	LANCL2	ENST00000952390.1		c.86C>T	p.Pro29Leu	missense	Exon 1 of 10	ENSP00000622449.1
	LANCL2	ENST00000952391.1		c.86C>T	p.Pro29Leu	missense	Exon 1 of 9	ENSP00000622450.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152254 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000599 AC: 1 AN: 166876 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000862

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000933 AC: 13 AN: 1392988 Hom.: 0 Cov.: 30 AF XY: 0.0000102 AC XY: 7 AN XY: 685940

African (AFR) AF: 0.0000327 AC: 1 AN: 30544

American (AMR) AF: 0.00 AC: 0 AN: 36240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24578

East Asian (EAS) AF: 0.000252 AC: 9 AN: 35644

South Asian (SAS) AF: 0.00 AC: 0 AN: 79010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 9.31e-7 AC: 1 AN: 1074478

Other (OTH) AF: 0.0000348 AC: 2 AN: 57404

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152254 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74382

African (AFR) AF: 0.00 AC: 0 AN: 41476

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.000229 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000844 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3476

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	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.75	N
PhyloP100		0.75
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.065
Sift	Benign	0.095	T
Sift4G	Uncertain	0.031	D
Polyphen		0.0030	B
Vest4		0.056
MVP		0.12
MPC		0.26
ClinPred		0.38	T
GERP RS		1.1
Varity_R		0.067
gMVP		0.52
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs374989248; hg19: chr7-55433804; COSMIC: COSV105037538;