10-101002729-G-A

Variant names:

• chr10-101002729-G-A
• rs772289024
• NM_001318100.2:c.191G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001318100.2(LZTS2):​c.191G>A​(p.Arg64Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,460,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: LZTS2 NM_001318100.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02
• Publications: 0 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11643624).
• BS2: High AC in GnomAdExome4 at 32 AD gene.

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.191G>A	p.Arg64Gln	missense	Exon 2 of 5	NP_001305029.1	Q9BRK4
	LZTS2	NM_001318099.2		c.191G>A	p.Arg64Gln	missense	Exon 2 of 5	NP_001305028.1	Q9BRK4
	LZTS2	NM_001394950.1		c.191G>A	p.Arg64Gln	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.191G>A	p.Arg64Gln	missense	Exon 2 of 5	ENSP00000416972.2	Q9BRK4
	LZTS2	ENST00000370220.1	TSL:1	c.191G>A	p.Arg64Gln	missense	Exon 1 of 4	ENSP00000359240.1	Q9BRK4
	LZTS2	ENST00000370223.7	TSL:1	c.191G>A	p.Arg64Gln	missense	Exon 2 of 5	ENSP00000359243.3	Q9BRK4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248960 AF XY: 0.00000742

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 32 AN: 1460390 Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17 AN XY: 726494

African (AFR) AF: 0.0000598 AC: 2 AN: 33464

American (AMR) AF: 0.0000224 AC: 1 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1111508

Other (OTH) AF: 0.0000166 AC: 1 AN: 60342

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.083
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.0
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.013
Sift	Benign	0.22	T
Sift4G	Benign	0.28	T
Polyphen		0.0040	B
Vest4		0.098
MutPred		0.44		Gain of relative solvent accessibility (P = 0.0507)
MVP		0.37
MPC		0.29
ClinPred		0.17	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.064
gMVP		0.32
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs772289024; hg19: chr10-102762486;