rs2272230

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001148.6(ANK2):​c.3893+60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,337,118 control chromosomes in the GnomAD database, including 14,857 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 5200 hom., cov: 32)
Exomes 𝑓: 0.11 ( 9657 hom. )

Consequence

ANK2
NM_001148.6 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.226

Publications

4 publications found
Variant links:
Genes affected
ANK2 (HGNC:493): (ankyrin 2) This gene encodes a member of the ankyrin family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton. Ankyrins play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. 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. The protein encoded by this gene is required for targeting and stability of Na/Ca exchanger 1 in cardiomyocytes. Mutations in this gene cause long QT syndrome 4 and cardiac arrhythmia syndrome. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Dec 2011]
ANK2 Gene-Disease associations (from GenCC):
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, ClinGen
  • Brugada syndrome
    Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Genomics England PanelApp, ClinGen
  • catecholaminergic polymorphic ventricular tachycardia
    Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp
  • heart conduction disease
    Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp
  • neurodevelopmental disorder
    Inheritance: AD Classification: LIMITED Submitted by: G2P
  • cardiac arrhythmia, ankyrin-B-related
    Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • long QT syndrome
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 4-113339382-C-T is Benign according to our data. Variant chr4-113339382-C-T is described in ClinVar as Benign. ClinVar VariationId is 1229699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001148.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ANK2
NM_001148.6
MANE Select
c.3893+60C>T
intron
N/ANP_001139.3
ANK2
NM_001386174.1
c.4034+60C>T
intron
N/ANP_001373103.1H0Y933
ANK2
NM_001386175.1
c.4010+60C>T
intron
N/ANP_001373104.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ANK2
ENST00000357077.9
TSL:1 MANE Select
c.3893+60C>T
intron
N/AENSP00000349588.4Q01484-4
ANK2
ENST00000506344.6
TSL:1
c.4034+60C>T
intron
N/AENSP00000422888.2H0Y933
ANK2
ENST00000394537.7
TSL:1
c.3893+60C>T
intron
N/AENSP00000378044.3Q01484-2

Frequencies

GnomAD3 genomes
AF:
0.203
AC:
30915
AN:
151928
Hom.:
5176
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.463
Gnomad AMI
AF:
0.0341
Gnomad AMR
AF:
0.148
Gnomad ASJ
AF:
0.0971
Gnomad EAS
AF:
0.116
Gnomad SAS
AF:
0.119
Gnomad FIN
AF:
0.0627
Gnomad MID
AF:
0.133
Gnomad NFE
AF:
0.101
Gnomad OTH
AF:
0.184
GnomAD4 exome
AF:
0.109
AC:
129364
AN:
1185072
Hom.:
9657
AF XY:
0.109
AC XY:
65767
AN XY:
603062
show subpopulations
African (AFR)
AF:
0.472
AC:
12944
AN:
27430
American (AMR)
AF:
0.137
AC:
6066
AN:
44174
Ashkenazi Jewish (ASJ)
AF:
0.101
AC:
2454
AN:
24400
East Asian (EAS)
AF:
0.124
AC:
4766
AN:
38330
South Asian (SAS)
AF:
0.125
AC:
9976
AN:
80092
European-Finnish (FIN)
AF:
0.0659
AC:
3441
AN:
52188
Middle Eastern (MID)
AF:
0.165
AC:
850
AN:
5164
European-Non Finnish (NFE)
AF:
0.0955
AC:
82329
AN:
861988
Other (OTH)
AF:
0.127
AC:
6538
AN:
51306
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
5387
10774
16162
21549
26936
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
2768
5536
8304
11072
13840
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.204
AC:
30983
AN:
152046
Hom.:
5200
Cov.:
32
AF XY:
0.199
AC XY:
14768
AN XY:
74334
show subpopulations
African (AFR)
AF:
0.464
AC:
19211
AN:
41446
American (AMR)
AF:
0.148
AC:
2254
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
0.0971
AC:
337
AN:
3470
East Asian (EAS)
AF:
0.116
AC:
602
AN:
5172
South Asian (SAS)
AF:
0.119
AC:
573
AN:
4826
European-Finnish (FIN)
AF:
0.0627
AC:
662
AN:
10566
Middle Eastern (MID)
AF:
0.136
AC:
40
AN:
294
European-Non Finnish (NFE)
AF:
0.101
AC:
6891
AN:
67974
Other (OTH)
AF:
0.181
AC:
382
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1073
2146
3219
4292
5365
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
292
584
876
1168
1460
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.131
Hom.:
7039
Bravo
AF:
0.222
Asia WGS
AF:
0.142
AC:
493
AN:
3478

ClinVar

ClinVar submissions
Significance:Benign
Revision:criteria provided, multiple submitters, no conflicts
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
-
2
not provided (2)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.48
DANN
Benign
0.61
PhyloP100
-0.23
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

Publications

Other links and lift over

dbSNP: rs2272230; hg19: chr4-114260538; API
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.