rs2025453

Positions:

• chr10-96471692-A-C
• chr10-96471692-A-T

Variant summary

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

The NM_012465.4(TLL2):​c.286+8657T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,094 control chromosomes in the GnomAD database, including 46,548 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 0.78 (46548 hom., cov: 31)
• Consequence: TLL2 NM_012465.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125

Genes affected

TLL2 (HGNC:11844): (tolloid like 2) This gene encodes an astacin-like zinc-dependent metalloprotease and is a subfamily member of the metzincin family. Unlike other family members, a similar protein in mice does not cleave procollagen C-propeptides or chordin. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLL2	NM_012465.4	c.286+8657T>G		intron_variant		ENST00000357947.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLL2	ENST00000357947.4	c.286+8657T>G		intron_variant		1	NM_012465.4	P1
TLL2	ENST00000469598.1	n.519+8657T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118563 AN: 151976 Hom.: 46507 Cov.: 31

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.780 AC: 118660 AN: 152094 Hom.: 46548 Cov.: 31 AF XY: 0.777 AC XY: 57811 AN XY: 74358

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.813

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.812

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.800

Alfa AF: 0.755 Hom.: 33975

Bravo AF: 0.797

Asia WGS AF: 0.861 AC: 2993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	8.4
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs2025453; hg19: chr10-98231449;