15-62762240-C-G

Position:

• chr15-62762240-C-G

Variant summary

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

The NM_015059.3(TLN2):​c.4780-32C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 1,612,076 control chromosomes in the GnomAD database, including 353,606 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 0.62 (29998 hom., cov: 31)
  • Exomes 𝑓: 0.66 (323608 hom.)
• Consequence: TLN2 NM_015059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLN2	NM_015059.3	c.4780-32C>G		intron_variant		ENST00000636159.2	NP_055874.2
TLN2	NM_001394547.1	c.4780-32C>G		intron_variant			NP_001381476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLN2	ENST00000636159.2	c.4780-32C>G		intron_variant		5	NM_015059.3	ENSP00000490662.2

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94208 AN: 151946 Hom.: 29986 Cov.: 31

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.644

GnomAD3 exomes AF: 0.632 AC: 158011 AN: 249992 Hom.: 50777 AF XY: 0.633 AC XY: 85520 AN XY: 135144

Gnomad AFR exome AF: 0.490

Gnomad AMR exome AF: 0.575

Gnomad ASJ exome AF: 0.608

Gnomad EAS exome AF: 0.532

Gnomad SAS exome AF: 0.560

Gnomad FIN exome AF: 0.751

Gnomad NFE exome AF: 0.685

Gnomad OTH exome AF: 0.645

GnomAD4 exome AF: 0.663 AC: 968291 AN: 1460012 Hom.: 323608 Cov.: 35 AF XY: 0.661 AC XY: 480102 AN XY: 726106

Gnomad4 AFR exome AF: 0.488

Gnomad4 AMR exome AF: 0.577

Gnomad4 ASJ exome AF: 0.609

Gnomad4 EAS exome AF: 0.553

Gnomad4 SAS exome AF: 0.556

Gnomad4 FIN exome AF: 0.752

Gnomad4 NFE exome AF: 0.683

Gnomad4 OTH exome AF: 0.644

GnomAD4 genome AF: 0.620 AC: 94256 AN: 152064 Hom.: 29998 Cov.: 31 AF XY: 0.619 AC XY: 46031 AN XY: 74350

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.644

Alfa AF: 0.606 Hom.: 3672

Bravo AF: 0.603

Asia WGS AF: 0.575 AC: 2000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.9
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2030040; hg19: chr15-63054439;