rs762091213

Variant names:

• chr10-101002662-C-A
• rs762091213
• NM_001318100.2:c.124C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-101002662-C-A
• chr10-101002662-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001318100.2(LZTS2):​c.124C>A​(p.Pro42Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,218 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. P42S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LZTS2 NM_001318100.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356
• Publications: 3 publications found

Genes affected

LZTS2 (HGNC:29381): (leucine zipper tumor suppressor 2) The protein encoded by this gene belongs to the leucine zipper tumor suppressor family of proteins, which function in transcription regulation and cell cycle control. This family member can repress beta-catenin-mediated transcriptional activation and is a negative regulator of the Wnt signaling pathway. It negatively regulates microtubule severing at centrosomes, and is necessary for central spindle formation and cytokinesis completion. It is implicated in cancer, where it may inhibit cell proliferation and decrease susceptibility to tumor development. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06585118).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318100.2. 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
	LZTS2	NM_001318100.2	MANE Select	c.124C>A	p.Pro42Thr	missense	Exon 2 of 5	NP_001305029.1	Q9BRK4
	LZTS2	NM_001318099.2		c.124C>A	p.Pro42Thr	missense	Exon 2 of 5	NP_001305028.1	Q9BRK4
	LZTS2	NM_001394950.1		c.124C>A	p.Pro42Thr	missense	Exon 2 of 5	NP_001381879.1	Q9BRK4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LZTS2	ENST00000454422.2	TSL:2 MANE Select	c.124C>A	p.Pro42Thr	missense	Exon 2 of 5	ENSP00000416972.2	Q9BRK4
	LZTS2	ENST00000370220.1	TSL:1	c.124C>A	p.Pro42Thr	missense	Exon 1 of 4	ENSP00000359240.1	Q9BRK4
	LZTS2	ENST00000370223.7	TSL:1	c.124C>A	p.Pro42Thr	missense	Exon 2 of 5	ENSP00000359243.3	Q9BRK4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1455732 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723676

African (AFR) AF: 0.00 AC: 0 AN: 33390

American (AMR) AF: 0.00 AC: 0 AN: 44336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25708

East Asian (EAS) AF: 0.00 AC: 0 AN: 39604

South Asian (SAS) AF: 0.00 AC: 0 AN: 85542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108816

Other (OTH) AF: 0.00 AC: 0 AN: 60178

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152218 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74378

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

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: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.9
DANN	Benign	0.96
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.36
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.059
Sift	Benign	0.074	T
Sift4G	Benign	0.24	T
Polyphen		0.19	B
Vest4		0.16
MutPred		0.20		Gain of phosphorylation at P42 (P = 0.0064)
MVP		0.48
MPC		0.28
ClinPred		0.072	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.082
gMVP		0.27
Mutation Taster		=93/7	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: rs762091213; hg19: chr10-102762419;