rs2303380

Variant names:

• chr11-113329987-G-A
• rs2303380
• NM_017868.4:c.504+8G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-113329987-G-A
• chr11-113329987-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017868.4(TTC12):​c.504+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 1,605,108 control chromosomes in the GnomAD database, including 317,243 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 0.63 (30800 hom., cov: 32)
  • Exomes 𝑓: 0.63 (286443 hom.)
• Consequence: TTC12 NM_017868.4 splice_region, intron
• Scores: Splicing: ADA: 0.00003587
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.506
• Publications: 36 publications found

Genes affected

TTC12 (HGNC:23700): (tetratricopeptide repeat domain 12) Involved in axonemal dynein complex assembly and sperm axoneme assembly. Located in centrosome and cytoplasm. Implicated in primary ciliary dyskinesia 45. [provided by Alliance of Genome Resources, Apr 2022]

TTC12 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 45

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-113329987-G-A is Benign according to our data. Variant chr11-113329987-G-A is described in ClinVar as Benign. ClinVar VariationId is 1287032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC12	NM_017868.4	c.504+8G>A		splice_region_variant, intron_variant	Intron 7 of 21	ENST00000529221.6	NP_060338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC12	ENST00000529221.6	c.504+8G>A		splice_region_variant, intron_variant	Intron 7 of 21	2	NM_017868.4	ENSP00000433757.1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96352 AN: 151940 Hom.: 30786 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.643

GnomAD2 exomes AF: 0.605 AC: 152147 AN: 251344 AF XY: 0.611

Gnomad AFR exome AF: 0.679

Gnomad AMR exome AF: 0.452

Gnomad ASJ exome AF: 0.657

Gnomad EAS exome AF: 0.529

Gnomad FIN exome AF: 0.685

Gnomad NFE exome AF: 0.635

Gnomad OTH exome AF: 0.624

GnomAD4 exome AF: 0.626 AC: 908914 AN: 1453048 Hom.: 286443 Cov.: 30 AF XY: 0.626 AC XY: 452668 AN XY: 723382

African (AFR) AF: 0.681 AC: 22685 AN: 33330

American (AMR) AF: 0.469 AC: 20944 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 17350 AN: 26066

East Asian (EAS) AF: 0.570 AC: 22601 AN: 39640

South Asian (SAS) AF: 0.604 AC: 52006 AN: 86082

European-Finnish (FIN) AF: 0.684 AC: 36525 AN: 53370

Middle Eastern (MID) AF: 0.639 AC: 3674 AN: 5752

European-Non Finnish (NFE) AF: 0.630 AC: 695101 AN: 1104060

Other (OTH) AF: 0.633 AC: 38028 AN: 60058

GnomAD4 genome AF: 0.634 AC: 96414 AN: 152060 Hom.: 30800 Cov.: 32 AF XY: 0.633 AC XY: 47051 AN XY: 74318

African (AFR) AF: 0.677 AC: 28082 AN: 41472

American (AMR) AF: 0.533 AC: 8148 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2241 AN: 3470

East Asian (EAS) AF: 0.541 AC: 2796 AN: 5170

South Asian (SAS) AF: 0.588 AC: 2833 AN: 4814

European-Finnish (FIN) AF: 0.678 AC: 7164 AN: 10564

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 43014 AN: 67982

Other (OTH) AF: 0.639 AC: 1348 AN: 2108

Alfa AF: 0.631 Hom.: 51589

Bravo AF: 0.624

Asia WGS AF: 0.544 AC: 1893 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Ciliary dyskinesia, primary, 45 Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
DANN	Benign	0.49
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000036
dbscSNV1_RF	Benign	0.0
Splicevardb		1.0
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

Other links and lift over

dbSNP: rs2303380; hg19: chr11-113200709; COSMIC: COSV59099317; COSMIC: COSV59099317;