rs2153522

Positions:

• chr10-60519054-G-A
• chr10-60519054-G-C
• chr10-60519054-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001204404.2(ANK3):​c.63+53411C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,042 control chromosomes in the GnomAD database, including 3,607 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 0.21 (3607 hom., cov: 32)
• Consequence: ANK3 NM_001204404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400

Genes affected

ANK3 (HGNC:494): (ankyrin 3) Ankyrins are a family of proteins that are believed to link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact, and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 3 is an immunologically distinct gene product from ankyrins 1 and 2, and was originally found at the axonal initial segment and nodes of Ranvier of neurons in the central and peripheral nervous systems. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK3	NM_001204404.2	c.63+53411C>T		intron_variant			NP_001191333.1
ANK3	NM_001204403.2	c.96+96132C>T		intron_variant			NP_001191332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000373827.6	c.96+96132C>T		intron_variant		1		ENSP00000362933.2
ANK3	ENST00000503366.6	c.63+53411C>T		intron_variant		2		ENSP00000425236.1
ANK3	ENST00000510382.1	n.102-10429C>T		intron_variant		2
ANK3	ENST00000622427.4	n.63+53411C>T		intron_variant		2		ENSP00000483244.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31815 AN: 151924 Hom.: 3602 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.209 AC: 31844 AN: 152042 Hom.: 3607 Cov.: 32 AF XY: 0.219 AC XY: 16267 AN XY: 74300

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.192

Alfa AF: 0.192 Hom.: 3987

Bravo AF: 0.210

Asia WGS AF: 0.347 AC: 1205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.78
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2153522; hg19: chr10-62278812;