15-62403872-C-T

Position:

• chr15-62403872-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015059.3(TLN2):​c.-238+13187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 152,212 control chromosomes in the GnomAD database, including 60,879 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 0.88 (60879 hom., cov: 32)
• Consequence: TLN2 NM_015059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLN2	NM_015059.3	c.-238+13187C>T		intron_variant		ENST00000636159.2	NP_055874.2
TLN2	NM_001394547.1	c.-113+13187C>T		intron_variant			NP_001381476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLN2	ENST00000636159.2	c.-238+13187C>T		intron_variant		5	NM_015059.3	ENSP00000490662	P1
TLN2	ENST00000561322.1	n.160+13187C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.882 AC: 134207 AN: 152094 Hom.: 60837 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 0.984

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.987

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.910

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

GnomAD4 genome AF: 0.882 AC: 134303 AN: 152212 Hom.: 60879 Cov.: 32 AF XY: 0.886 AC XY: 65912 AN XY: 74428

Gnomad4 AFR AF: 0.646

Gnomad4 AMR AF: 0.943

Gnomad4 ASJ AF: 0.984

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.987

Gnomad4 FIN AF: 0.982

Gnomad4 NFE AF: 0.973

Gnomad4 OTH AF: 0.911

Alfa AF: 0.939 Hom.: 13768

Bravo AF: 0.867

Asia WGS AF: 0.968 AC: 3366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.93
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs290297; hg19: chr15-62696071;