15-62657763-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015059.3(TLN2):c.661-8T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,609,128 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 23 hom. )

Consequence

TLN2
NM_015059.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002717

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.797

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 15-62657763-T-C is Benign according to our data. Variant chr15-62657763-T-C is described in ClinVar as [Benign]. Clinvar id is 771473.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0014 (2036/1456832) while in subpopulation AMR AF= 0.0174 (753/43348). AF 95% confidence interval is 0.0163. There are 23 homozygotes in gnomad4_exome. There are 975 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd at 246 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLN2	NM_015059.3 linkuse as main transcript	c.661-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000636159.2
TLN2	NM_001394547.1 linkuse as main transcript	c.661-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
TLN2	ENST00000636159.2 linkuse as main transcript	c.661-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5	NM_015059.3	P1
TLN2	ENST00000561311.5 linkuse as main transcript	c.661-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5		P1
TLN2	ENST00000474847.2 linkuse as main transcript	n.610-8T>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

246

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00812

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00984

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00360

AC:

879

AN:

243986

Hom.:

AF XY:

0.00306

AC XY:

403

AN XY:

131778

show subpopulations

Gnomad AFR exome

AF:

0.000867

Gnomad AMR exome

AF:

0.0190

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00862

Gnomad SAS exome

AF:

0.000140

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.000313

Gnomad OTH exome

AF:

0.00454

GnomAD4 exome

AF:

0.00140

AC:

2036

AN:

1456832

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

975

AN XY:

724604

show subpopulations

Gnomad4 AFR exome

AF:

0.000604

Gnomad4 AMR exome

AF:

0.0174

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0160

Gnomad4 SAS exome

AF:

0.000236

Gnomad4 FIN exome

AF:

0.00118

Gnomad4 NFE exome

AF:

0.000416

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.00162

AC:

247

AN:

152296

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

117

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00824

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00967

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000850

Hom.:

Bravo

AF:

0.00246

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

Cadd

Benign

Dann

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00027

dbscSNV1_RF

Benign

0.038

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over