rs2456462

Variant names:

• chr15-62502057-G-A
• rs2456462
• NM_015059.3:c.-237-87630G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-62502057-G-A
• chr15-62502057-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015059.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLN2	NM_015059.3	MANE Select	c.-237-87630G>A		intron	N/A	NP_055874.2	Q9Y4G6
	TLN2	NM_001394547.1		c.-112-87630G>A		intron	N/A	NP_001381476.1	Q9Y4G6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLN2	ENST00000636159.2	TSL:5 MANE Select	c.-237-87630G>A		intron	N/A	ENSP00000490662.2	Q9Y4G6
	TLN2	ENST00000895916.1		c.-112-87630G>A		intron	N/A	ENSP00000565975.1
	TLN2	ENST00000964497.1		c.-193-54441G>A		intron	N/A	ENSP00000634556.1

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

African (AFR) AF: 0.0908 AC: 3770 AN: 41512

American (AMR) AF: 0.238 AC: 3641 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3472

East Asian (EAS) AF: 0.531 AC: 2736 AN: 5156

South Asian (SAS) AF: 0.310 AC: 1497 AN: 4822

European-Finnish (FIN) AF: 0.157 AC: 1657 AN: 10570

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9979 AN: 68000

Other (OTH) AF: 0.171 AC: 362 AN: 2112

Alfa AF: 0.162 Hom.: 2162

Bravo AF: 0.164

Asia WGS AF: 0.378 AC: 1308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.9
DANN	Benign	0.67
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs2456462; hg19: chr15-62794256;