15-62400579-G-T

Variant names:

• chr15-62400579-G-T
• rs460458
• NM_015059.3:c.-238+9894G>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.-238+9894G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,098 control chromosomes in the GnomAD database, including 51,675 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 0.82 (51675 hom., cov: 32)
• Consequence: TLN2 NM_015059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 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.-238+9894G>T		intron	N/A	NP_055874.2	Q9Y4G6
	TLN2	NM_001394547.1		c.-113+9894G>T		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.-238+9894G>T		intron	N/A	ENSP00000490662.2	Q9Y4G6
	TLN2	ENST00000895916.1		c.-113+9894G>T		intron	N/A	ENSP00000565975.1
	TLN2	ENST00000964497.1		c.-194+9894G>T		intron	N/A	ENSP00000634556.1

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124704 AN: 151980 Hom.: 51635 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.833

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

GnomAD4 genome AF: 0.821 AC: 124803 AN: 152098 Hom.: 51675 Cov.: 32 AF XY: 0.824 AC XY: 61252 AN XY: 74346

African (AFR) AF: 0.699 AC: 28944 AN: 41418

American (AMR) AF: 0.879 AC: 13442 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3048 AN: 3472

East Asian (EAS) AF: 0.909 AC: 4700 AN: 5170

South Asian (SAS) AF: 0.878 AC: 4231 AN: 4818

European-Finnish (FIN) AF: 0.883 AC: 9364 AN: 10604

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.857 AC: 58249 AN: 68004

Other (OTH) AF: 0.836 AC: 1767 AN: 2114

Alfa AF: 0.845 Hom.: 41309

Bravo AF: 0.815

Asia WGS AF: 0.883 AC: 3067 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.59
DANN	Benign	0.47
PhyloP100		-0.14

Splicing

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

Other links and lift over

dbSNP: rs460458; hg19: chr15-62692778;