13-20981461-T-C

Variant names:

• chr13-20981461-T-C
• rs56244446
• NM_014572.3:c.2665+5A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_014572.3(LATS2):​c.2665+5A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,612,078 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (21 hom.)
• Consequence: LATS2 NM_014572.3 splice_region, intron
• Scores: Splicing: ADA: 0.0005560
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.463
• Publications: 2 publications found

Genes affected

LATS2 (HGNC:6515): (large tumor suppressor kinase 2) This gene encodes a serine/threonine protein kinase belonging to the LATS tumor suppressor family. The protein localizes to centrosomes during interphase, and early and late metaphase. It interacts with the centrosomal proteins aurora-A and ajuba and is required for accumulation of gamma-tubulin and spindle formation at the onset of mitosis. It also interacts with a negative regulator of p53 and may function in a positive feedback loop with p53 that responds to cytoskeleton damage. Additionally, it can function as a co-repressor of androgen-responsive gene expression. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 13-20981461-T-C is Benign according to our data. Variant chr13-20981461-T-C is described in ClinVar as [Benign]. Clinvar id is 784478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00131 (1919/1459752) while in subpopulation AMR AF = 0.0236 (1051/44538). AF 95% confidence interval is 0.0224. There are 21 homozygotes in GnomAdExome4. There are 825 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 389 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LATS2	NM_014572.3	c.2665+5A>G		splice_region_variant, intron_variant	Intron 6 of 7	ENST00000382592.5	NP_055387.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LATS2	ENST00000382592.5	c.2665+5A>G		splice_region_variant, intron_variant	Intron 6 of 7	1	NM_014572.3	ENSP00000372035.4

Frequencies

GnomAD3 genomes AF: 0.00252 AC: 384 AN: 152208 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00479 AC: 1194 AN: 249174 AF XY: 0.00373

Gnomad AFR exome AF: 0.000739

Gnomad AMR exome AF: 0.0253

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0149

Gnomad FIN exome AF: 0.0000931

Gnomad NFE exome AF: 0.000116

Gnomad OTH exome AF: 0.00296

GnomAD4 exome AF: 0.00131 AC: 1919 AN: 1459752 Hom.: 21 Cov.: 31 AF XY: 0.00114 AC XY: 825 AN XY: 726096

African (AFR) AF: 0.000598 AC: 20 AN: 33438

American (AMR) AF: 0.0236 AC: 1051 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25942

East Asian (EAS) AF: 0.0164 AC: 652 AN: 39684

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86064

European-Finnish (FIN) AF: 0.0000376 AC: 2 AN: 53226

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

European-Non Finnish (NFE) AF: 0.0000810 AC: 90 AN: 1110832

Other (OTH) AF: 0.00153 AC: 92 AN: 60290

GnomAD4 genome AF: 0.00255 AC: 389 AN: 152326 Hom.: 7 Cov.: 32 AF XY: 0.00285 AC XY: 212 AN XY: 74502

African (AFR) AF: 0.00123 AC: 51 AN: 41576

American (AMR) AF: 0.0153 AC: 234 AN: 15300

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

East Asian (EAS) AF: 0.0155 AC: 80 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68034

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00122 Hom.: 3

Bravo AF: 0.00461

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.0
DANN	Benign	0.48
PhyloP100		0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00056
dbscSNV1_RF	Benign	0.034
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: rs56244446; hg19: chr13-21555600;