rs2393607

Variant names:

• chr10-60042803-G-T
• rs2393607
• NM_020987.5:c.13066-44C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-60042803-G-T
• chr10-60042803-G-A

Variant summary

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

The NM_020987.5(ANK3):​c.13066-44C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 1,604,790 control chromosomes in the GnomAD database, including 461,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (40096 hom., cov: 32)
  • Exomes 𝑓: 0.76 (421091 hom.)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.699
• Publications: 5 publications found

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]

ANK3 Gene-Disease associations (from GenCC):

• intellectual disability-hypotonia-spasticity-sleep disorder syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• intellectual disability

  Inheritance: AR, AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000232682 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-60042803-G-T is Benign according to our data. Variant chr10-60042803-G-T is described in ClinVar as Benign. ClinVar VariationId is 1192428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020987.5. 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
	ANK3	NM_020987.5	MANE Select	c.13066-44C>A		intron	N/A	NP_066267.2
	ANK3	NM_001204404.2		c.5539-44C>A		intron	N/A	NP_001191333.1	Q12955-4
	ANK3	NM_001320874.2		c.5536-44C>A		intron	N/A	NP_001307803.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	ENST00000280772.7	TSL:1 MANE Select	c.13066-44C>A		intron	N/A	ENSP00000280772.1	Q12955-3
	ANK3	ENST00000373827.6	TSL:1	c.5518-44C>A		intron	N/A	ENSP00000362933.2	Q12955-5
	ANK3	ENST00000355288.6	TSL:1	c.2938-44C>A		intron	N/A	ENSP00000347436.2	Q12955-6

Frequencies

GnomAD3 genomes AF: 0.762 AC: 109868 AN: 144186 Hom.: 40085 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.777

GnomAD2 exomes AF: 0.726 AC: 180923 AN: 249058 AF XY: 0.733

Gnomad AFR exome AF: 0.662

Gnomad AMR exome AF: 0.566

Gnomad ASJ exome AF: 0.787

Gnomad EAS exome AF: 0.823

Gnomad FIN exome AF: 0.693

Gnomad NFE exome AF: 0.772

Gnomad OTH exome AF: 0.725

GnomAD4 exome AF: 0.758 AC: 1106365 AN: 1460506 Hom.: 421091 Cov.: 48 AF XY: 0.757 AC XY: 549935 AN XY: 726562

African (AFR) AF: 0.653 AC: 21802 AN: 33404

American (AMR) AF: 0.574 AC: 25579 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 20562 AN: 26080

East Asian (EAS) AF: 0.785 AC: 31140 AN: 39664

South Asian (SAS) AF: 0.714 AC: 61476 AN: 86080

European-Finnish (FIN) AF: 0.687 AC: 36654 AN: 53340

Middle Eastern (MID) AF: 0.747 AC: 4301 AN: 5760

European-Non Finnish (NFE) AF: 0.773 AC: 859535 AN: 1111298

Other (OTH) AF: 0.751 AC: 45316 AN: 60332

GnomAD4 genome AF: 0.762 AC: 109921 AN: 144284 Hom.: 40096 Cov.: 32 AF XY: 0.761 AC XY: 53667 AN XY: 70480

African (AFR) AF: 0.702 AC: 26962 AN: 38402

American (AMR) AF: 0.738 AC: 10334 AN: 14000

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2731 AN: 3382

East Asian (EAS) AF: 0.839 AC: 4242 AN: 5058

South Asian (SAS) AF: 0.766 AC: 3480 AN: 4546

European-Finnish (FIN) AF: 0.737 AC: 7226 AN: 9804

Middle Eastern (MID) AF: 0.761 AC: 216 AN: 284

European-Non Finnish (NFE) AF: 0.796 AC: 52495 AN: 65914

Other (OTH) AF: 0.777 AC: 1567 AN: 2016

Alfa AF: 0.720 Hom.: 12327

Bravo AF: 0.717

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Intellectual disability-hypotonia-spasticity-sleep disorder syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.3
DANN	Benign	0.72
PhyloP100		0.70
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: rs2393607; hg19: chr10-61802561;