10-96370242-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_012465.4(TLL2):c.2736C>T(p.Asn912=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00449 in 1,613,526 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (21 hom.)
• Consequence: TLL2 NM_012465.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.36

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 10-96370242-G-A is Benign according to our data. Variant chr10-96370242-G-A is described in ClinVar as [Benign]. Clinvar id is 714624.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLL2	NM_012465.4	c.2736C>T	p.Asn912=	synonymous_variant	20/21	ENST00000357947.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLL2	ENST00000357947.4	c.2736C>T	p.Asn912=	synonymous_variant	20/21	1	NM_012465.4	P1

Frequencies

GnomAD3 genomes AF: 0.00362 AC: 551 AN: 152264 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0138

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00473

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00431 AC: 1077 AN: 250160 Hom.: 5 AF XY: 0.00419 AC XY: 567 AN XY: 135190

Gnomad AFR exome AF: 0.000862

Gnomad AMR exome AF: 0.00143

Gnomad ASJ exome AF: 0.00230

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00171

Gnomad FIN exome AF: 0.0137

Gnomad NFE exome AF: 0.00542

Gnomad OTH exome AF: 0.00492

GnomAD4 exome AF: 0.00458 AC: 6690 AN: 1461144 Hom.: 21 Cov.: 31 AF XY: 0.00444 AC XY: 3227 AN XY: 726830

Gnomad4 AFR exome AF: 0.000538

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.00238

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00178

Gnomad4 FIN exome AF: 0.0138

Gnomad4 NFE exome AF: 0.00492

Gnomad4 OTH exome AF: 0.00311

GnomAD4 genome AF: 0.00362 AC: 551 AN: 152382 Hom.: 4 Cov.: 32 AF XY: 0.00372 AC XY: 277 AN XY: 74522

Gnomad4 AFR AF: 0.000673

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0138

Gnomad4 NFE AF: 0.00473

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00369 Hom.: 0

Bravo AF: 0.00280

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00382

EpiControl AF: 0.00404

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	8.8
Dann	Benign	0.93

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: rs41291626; hg19: chr10-98129999;