chr17-63049777-A-C

Variant names:

• chr17-63049777-A-C
• rs186419369
• NM_001394998.1:c.68-24166A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001394998.1(TANC2):​c.68-24166A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 152,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.0017 (0 hom., cov: 31)
• Consequence: TANC2 NM_001394998.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.469
• Publications: 0 publications found

Genes affected

TANC2 (HGNC:30212): (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2) Predicted to be involved in dense core granule cytoskeletal transport; regulation of dendritic spine development; and regulation of dendritic spine morphogenesis. Predicted to act upstream of or within in utero embryonic development. Located in dendritic spine. [provided by Alliance of Genome Resources, Apr 2022]

TANC2 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with autistic features and language delay, with or without seizures

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-63049777-A-C is Benign according to our data. Variant chr17-63049777-A-C is described in ClinVar as [Benign]. Clinvar id is 2648033.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0017 (259/152308) while in subpopulation AFR AF = 0.00553 (230/41572). AF 95% confidence interval is 0.00495. There are 0 homozygotes in GnomAd4. There are 123 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 259 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANC2	NM_001394998.1	c.68-24166A>C		intron_variant	Intron 2 of 27	ENST00000689528.1	NP_001381927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANC2	ENST00000689528.1	c.68-24166A>C		intron_variant	Intron 2 of 27		NM_001394998.1	ENSP00000510600.1
TANC2	ENST00000424789.6	c.68-24166A>C		intron_variant	Intron 1 of 24	1		ENSP00000387593.2
TANC2	ENST00000389520.8	c.68-24166A>C		intron_variant	Intron 1 of 25	5		ENSP00000374171.4

Frequencies

GnomAD3 genomes AF: 0.00170 AC: 259 AN: 152190 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00191

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

GnomAD4 genome AF: 0.00170 AC: 259 AN: 152308 Hom.: 0 Cov.: 31 AF XY: 0.00165 AC XY: 123 AN XY: 74488

African (AFR) AF: 0.00553 AC: 230 AN: 41572

American (AMR) AF: 0.00163 AC: 25 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00166 Hom.: 1

Bravo AF: 0.00220

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TANC2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	19
DANN	Benign	0.66
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: 10

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

Other links and lift over

dbSNP: rs186419369; hg19: chr17-61127138;