chr15-62657763-T-C

Position:

• chr15-62657763-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.797

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]

ACMG classification

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 247 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLN2	NM_015059.3	c.661-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000636159.2	NP_055874.2
TLN2	NM_001394547.1	c.661-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001381476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLN2	ENST00000636159.2	c.661-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_015059.3	ENSP00000490662	P1
TLN2	ENST00000561311.5	c.661-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000453508	P1
TLN2	ENST00000474847.2	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.: 0 Cov.: 32

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.: 9 AF XY: 0.00306 AC XY: 403 AN XY: 131778

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.: 23 Cov.: 30 AF XY: 0.00135 AC XY: 975 AN XY: 724604

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.: 1 Cov.: 32 AF XY: 0.00157 AC XY: 117 AN XY: 74470

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.: 0

Bravo AF: 0.00246

Asia WGS AF: 0.00953 AC: 33 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
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

Other links and lift over

dbSNP: rs140451649; hg19: chr15-62949962;