15-62762240-C-G

Variant names:

• chr15-62762240-C-G
• rs2030040
• NM_015059.3:c.4780-32C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.8).
• 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 rank	MANE	Protein	UniProt
TLN2	NM_015059.3	c.4780-32C>G		intron_variant	Intron 38 of 58	ENST00000636159.2	NP_055874.2
TLN2	NM_001394547.1	c.4780-32C>G		intron_variant	Intron 37 of 57		NP_001381476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLN2	ENST00000636159.2	c.4780-32C>G		intron_variant	Intron 38 of 58	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

GnomAD2 exomes AF: 0.632 AC: 158011 AN: 249992 AF XY: 0.633

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 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

African (AFR) AF: 0.488 AC: 16303 AN: 33436

American (AMR) AF: 0.577 AC: 25807 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 15882 AN: 26064

East Asian (EAS) AF: 0.553 AC: 21945 AN: 39670

South Asian (SAS) AF: 0.556 AC: 47942 AN: 86152

European-Finnish (FIN) AF: 0.752 AC: 40151 AN: 53380

Middle Eastern (MID) AF: 0.566 AC: 3239 AN: 5718

European-Non Finnish (NFE) AF: 0.683 AC: 758178 AN: 1110566

Other (OTH) AF: 0.644 AC: 38844 AN: 60316

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

African (AFR) AF: 0.496 AC: 20571 AN: 41456

American (AMR) AF: 0.602 AC: 9201 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2124 AN: 3472

East Asian (EAS) AF: 0.534 AC: 2760 AN: 5166

South Asian (SAS) AF: 0.564 AC: 2715 AN: 4816

European-Finnish (FIN) AF: 0.758 AC: 8035 AN: 10596

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46620 AN: 67968

Other (OTH) AF: 0.644 AC: 1361 AN: 2112

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
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2030040; hg19: chr15-63054439; COSMIC: COSV107393145; COSMIC: COSV107393145;