15-62395140-C-T

Variant names:

• chr15-62395140-C-T
• rs2456930
• NM_015059.3:c.-238+4455C>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+4455C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 149,432 control chromosomes in the GnomAD database, including 15,254 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 0.44 (15254 hom., cov: 26)
• Consequence: TLN2 NM_015059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• Publications: 11 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLN2	NM_015059.3	c.-238+4455C>T		intron_variant	Intron 1 of 58	ENST00000636159.2	NP_055874.2
TLN2	NM_001394547.1	c.-113+4455C>T		intron_variant	Intron 1 of 57		NP_001381476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLN2	ENST00000636159.2	c.-238+4455C>T		intron_variant	Intron 1 of 58	5	NM_015059.3	ENSP00000490662.2
TLN2	ENST00000561322.1	n.160+4455C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.445 AC: 66392 AN: 149314 Hom.: 15231 Cov.: 26

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.445 AC: 66468 AN: 149432 Hom.: 15254 Cov.: 26 AF XY: 0.451 AC XY: 32786 AN XY: 72744

African (AFR) AF: 0.473 AC: 19106 AN: 40430

American (AMR) AF: 0.533 AC: 7889 AN: 14794

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1108 AN: 3454

East Asian (EAS) AF: 0.712 AC: 3625 AN: 5088

South Asian (SAS) AF: 0.541 AC: 2487 AN: 4596

European-Finnish (FIN) AF: 0.435 AC: 4437 AN: 10204

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.391 AC: 26462 AN: 67606

Other (OTH) AF: 0.429 AC: 883 AN: 2058

Alfa AF: 0.415 Hom.: 42841

Bravo AF: 0.455

Asia WGS AF: 0.624 AC: 2168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.79
PhyloP100		0.035

Splicing

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

Other links and lift over

dbSNP: rs2456930; hg19: chr15-62687339;