rs7210972

Variant names:

• chr17-63155117-A-G
• rs7210972
• NM_001394998.1:c.433+3737A>G

Variant summary

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

The NM_001394998.1(TANC2):​c.433+3737A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,604 control chromosomes in the GnomAD database, including 25,493 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 0.56 (25493 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: TANC2 NM_001394998.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525
• Publications: 9 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 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.433+3737A>G		intron	N/A	NP_001381927.1	A0A8I5KXR5
	TANC2	NM_001411076.1		c.212-38874A>G		intron	N/A	NP_001398005.1	Q9HCD6-2
	TANC2	NM_025185.4		c.212-38874A>G		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.433+3737A>G		intron	N/A	ENSP00000510600.1	A0A8I5KXR5
	TANC2	ENST00000424789.6	TSL:1	c.212-38874A>G		intron	N/A	ENSP00000387593.2	Q9HCD6-1
	TANC2	ENST00000389520.8	TSL:5	c.212-38874A>G		intron	N/A	ENSP00000374171.4	Q9HCD6-2

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85469 AN: 151486 Hom.: 25450 Cov.: 30

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.510

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.564 AC: 85571 AN: 151604 Hom.: 25493 Cov.: 30 AF XY: 0.561 AC XY: 41501 AN XY: 74034

African (AFR) AF: 0.745 AC: 30790 AN: 41340

American (AMR) AF: 0.465 AC: 7073 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1649 AN: 3470

East Asian (EAS) AF: 0.172 AC: 886 AN: 5160

South Asian (SAS) AF: 0.491 AC: 2362 AN: 4812

European-Finnish (FIN) AF: 0.570 AC: 5986 AN: 10510

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35063 AN: 67780

Other (OTH) AF: 0.513 AC: 1080 AN: 2104

Alfa AF: 0.526 Hom.: 11678

Bravo AF: 0.560

Asia WGS AF: 0.409 AC: 1421 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.67
PhyloP100		-0.53
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: rs7210972; hg19: chr17-61232478;