rs3816988

Variant names:

• chr15-62819540-T-C
• rs3816988
• NM_015059.3:c.6796T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-62819540-T-C
• chr15-62819540-T-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.6796T>C​(p.Phe2266Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,613,722 control chromosomes in the GnomAD database, including 24,417 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2416 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22001 hom.)
• Consequence: TLN2 NM_015059.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 27 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 (MetaRNN=8.6405873E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLN2	NM_015059.3	c.6796T>C	p.Phe2266Leu	missense_variant	Exon 53 of 59	ENST00000636159.2	NP_055874.2
TLN2	NM_001394547.1	c.6796T>C	p.Phe2266Leu	missense_variant	Exon 52 of 58		NP_001381476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLN2	ENST00000636159.2	c.6796T>C	p.Phe2266Leu	missense_variant	Exon 53 of 59	5	NM_015059.3	ENSP00000490662.2
TLN2	ENST00000489129.5	n.4711T>C		non_coding_transcript_exon_variant	Exon 21 of 27	1
TLN2	ENST00000561311.5	c.6796T>C	p.Phe2266Leu	missense_variant	Exon 52 of 58	5		ENSP00000453508.1
TLN2	ENST00000494733.5	c.3538T>C	p.Phe1180Leu	missense_variant	Exon 26 of 32	5		ENSP00000453730.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26622 AN: 152046 Hom.: 2408 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.0764

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.162

GnomAD2 exomes AF: 0.162 AC: 40783 AN: 251090 AF XY: 0.165

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.0738

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.171 AC: 249884 AN: 1461558 Hom.: 22001 Cov.: 32 AF XY: 0.172 AC XY: 124736 AN XY: 727096

African (AFR) AF: 0.200 AC: 6710 AN: 33474

American (AMR) AF: 0.146 AC: 6512 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 4938 AN: 26134

East Asian (EAS) AF: 0.0780 AC: 3097 AN: 39694

South Asian (SAS) AF: 0.207 AC: 17829 AN: 86242

European-Finnish (FIN) AF: 0.143 AC: 7624 AN: 53306

Middle Eastern (MID) AF: 0.198 AC: 1140 AN: 5768

European-Non Finnish (NFE) AF: 0.172 AC: 191159 AN: 1111830

Other (OTH) AF: 0.180 AC: 10875 AN: 60386

GnomAD4 genome AF: 0.175 AC: 26663 AN: 152164 Hom.: 2416 Cov.: 32 AF XY: 0.175 AC XY: 13017 AN XY: 74392

African (AFR) AF: 0.196 AC: 8130 AN: 41508

American (AMR) AF: 0.180 AC: 2748 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3472

East Asian (EAS) AF: 0.0764 AC: 395 AN: 5172

South Asian (SAS) AF: 0.206 AC: 994 AN: 4816

European-Finnish (FIN) AF: 0.148 AC: 1565 AN: 10600

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11568 AN: 68004

Other (OTH) AF: 0.166 AC: 351 AN: 2114

Alfa AF: 0.168 Hom.: 9967

Bravo AF: 0.176

TwinsUK AF: 0.186 AC: 689

ALSPAC AF: 0.181 AC: 699

ESP6500AA AF: 0.193 AC: 851

ESP6500EA AF: 0.171 AC: 1472

ExAC AF: 0.164 AC: 19893

EpiCase AF: 0.164

EpiControl AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.31	T;T;T
MetaRNN	Benign	0.00086	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;.;.
PhyloP100		2.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	1.4	N;.;N
Sift	Benign	0.40	T;.;T
Sift4G	Benign	0.36	T;.;T
Polyphen		0.0	B;.;.
Vest4		0.024
MutPred		0.18		Loss of methylation at K2267 (P = 0.0684);.;.;
MPC		0.26
ClinPred		0.018	T
GERP RS		4.6
Varity_R		0.078
gMVP		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3816988; hg19: chr15-63111739; COSMIC: COSV60888929; COSMIC: COSV60888929;