rs12913538

Variant names:

• chr15-62606961-G-A
• rs12913538
• NM_015059.3:c.-161-11390G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-62606961-G-A
• chr15-62606961-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015059.3(TLN2):​c.-161-11390G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,830 control chromosomes in the GnomAD database, including 10,464 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10464 hom., cov: 31)
• Consequence: TLN2 NM_015059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 5 publications found

Genes affected

TLN2 (HGNC:15447): (talin 2) This gene encodes a protein related to talin 1, a cytoskeletal protein that plays a significant role in the assembly of actin filaments and in spreading and migration of various cell types, including fibroblasts and osteoclasts. This protein has a different pattern of expression compared to talin 1 but, like talin 1, is thought to associate with unique transmembrane receptors to form novel linkages between extracellular matrices and the actin cytoskeleton. [provided by RefSeq, Jul 2008]

TLN2 Gene-Disease associations (from GenCC):

• camptodactyly of fingers

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLN2	NM_015059.3	c.-161-11390G>A		intron_variant	Intron 2 of 58	ENST00000636159.2	NP_055874.2
TLN2	NM_001394547.1	c.-37+17199G>A		intron_variant	Intron 2 of 57		NP_001381476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLN2	ENST00000636159.2	c.-161-11390G>A		intron_variant	Intron 2 of 58	5	NM_015059.3	ENSP00000490662.2
TLN2	ENST00000561311.5	c.-37+17199G>A		intron_variant	Intron 2 of 57	5		ENSP00000453508.1
TLN2	ENST00000561197.5	n.227-11390G>A		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55333 AN: 151712 Hom.: 10455 Cov.: 31

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.355

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.365 AC: 55389 AN: 151830 Hom.: 10464 Cov.: 31 AF XY: 0.372 AC XY: 27632 AN XY: 74202

African (AFR) AF: 0.393 AC: 16277 AN: 41404

American (AMR) AF: 0.380 AC: 5798 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 951 AN: 3468

East Asian (EAS) AF: 0.584 AC: 3002 AN: 5138

South Asian (SAS) AF: 0.489 AC: 2345 AN: 4798

European-Finnish (FIN) AF: 0.411 AC: 4334 AN: 10538

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.318 AC: 21580 AN: 67920

Other (OTH) AF: 0.353 AC: 744 AN: 2108

Alfa AF: 0.334 Hom.: 3273

Bravo AF: 0.360

Asia WGS AF: 0.485 AC: 1684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.71
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs12913538; hg19: chr15-62899160;