rs2447442

Variant names:

• chr17-63240716-C-T
• rs2447442
• NM_001394998.1:c.1033+2639C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394998.1(TANC2):​c.1033+2639C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,014 control chromosomes in the GnomAD database, including 28,986 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 0.59 (28986 hom., cov: 32)
• Consequence: TANC2 NM_001394998.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887
• Publications: 8 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: ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000233635 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394998.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANC2	NM_001394998.1	MANE Select	c.1033+2639C>T		intron	N/A	NP_001381927.1	A0A8I5KXR5
	TANC2	NM_001411076.1		c.811+2639C>T		intron	N/A	NP_001398005.1	Q9HCD6-2
	TANC2	NM_025185.4		c.811+2639C>T		intron	N/A	NP_079461.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TANC2	ENST00000689528.1	MANE Select	c.1033+2639C>T		intron	N/A	ENSP00000510600.1	A0A8I5KXR5
	TANC2	ENST00000424789.6	TSL:1	c.811+2639C>T		intron	N/A	ENSP00000387593.2	Q9HCD6-1
	TANC2	ENST00000583356.5	TSL:1	c.595+2639C>T		intron	N/A	ENSP00000462109.1	J3KRP9

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89985 AN: 151896 Hom.: 28932 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.593 AC: 90096 AN: 152014 Hom.: 28986 Cov.: 32 AF XY: 0.588 AC XY: 43650 AN XY: 74272

African (AFR) AF: 0.844 AC: 35033 AN: 41484

American (AMR) AF: 0.475 AC: 7257 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1657 AN: 3462

East Asian (EAS) AF: 0.174 AC: 897 AN: 5152

South Asian (SAS) AF: 0.493 AC: 2373 AN: 4812

European-Finnish (FIN) AF: 0.569 AC: 6017 AN: 10566

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35050 AN: 67964

Other (OTH) AF: 0.535 AC: 1127 AN: 2108

Alfa AF: 0.535 Hom.: 11448

Bravo AF: 0.593

Asia WGS AF: 0.410 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.70
DANN	Benign	0.34
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2447442; hg19: chr17-61318077; COSMIC: COSV67340691;