rs12913538

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TLN2	NM_015059.3	c.-161-11390G>A		intron_variant		ENST00000636159.2	NP_055874.2
TLN2	NM_001394547.1	c.-37+17199G>A		intron_variant			NP_001381476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLN2	ENST00000636159.2	c.-161-11390G>A		intron_variant		5	NM_015059.3	ENSP00000490662	P1
TLN2	ENST00000561311.5	c.-37+17199G>A		intron_variant		5		ENSP00000453508	P1
TLN2	ENST00000561197.5	n.227-11390G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.353

Alfa AF: 0.336 Hom.: 2630

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12913538; hg19: chr15-62899160;