rs2456462

chr15-62502057-G-Achr15-62502057-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015059.3(TLN2):c.-237-87630G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,134 control chromosomes in the GnomAD database, including 2,533 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 0.16 (2533 hom., cov: 33)
• Consequence: TLN2 NM_015059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLN2	NM_015059.3	c.-237-87630G>A		intron_variant		ENST00000636159.2
TLN2	NM_001394547.1	c.-112-87630G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLN2	ENST00000636159.2	c.-237-87630G>A		intron_variant		5	NM_015059.3	P1
TLN2	ENST00000561197.5	n.150+48316G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24260 AN: 152016 Hom.: 2530 Cov.: 33

Gnomad AFR AF: 0.0910

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.160 AC: 24266 AN: 152134 Hom.: 2533 Cov.: 33 AF XY: 0.167 AC XY: 12442 AN XY: 74372

Gnomad4 AFR AF: 0.0908

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.171

Alfa AF: 0.158 Hom.: 1211

Bravo AF: 0.164

Asia WGS AF: 0.378 AC: 1308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.9
Dann	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2456462; hg19: chr15-62794256;