rs143032902
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4BP6
The NM_206933.4(USH2A):c.13622A>C(p.Gln4541Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Q4541Q) has been classified as Likely benign. The gene USH2A is included in the ClinGen Criteria Specification Registry.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
USH2A
NM_206933.4 missense
NM_206933.4 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 2.01
Publications
1 publications found
Genes affected
USH2A (HGNC:12601): (usherin) This gene encodes a protein that contains laminin EGF motifs, a pentaxin domain, and many fibronectin type III motifs. The protein is found in the basement membrane, and may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIa and retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]
USH2A Gene-Disease associations (from GenCC):
- Usher syndrome type 2AInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- Usher syndrome type 2Inheritance: Unknown, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- retinitis pigmentosa 39Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- retinitis pigmentosaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Specifications for USH2A are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.29065925).
BP6
Variant 1-215674289-T-G is Benign according to our data. Variant chr1-215674289-T-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 48420.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_206933.4. You can select a different transcript below to see updated ACMG assignments.
Frequencies
GnomAD3 genomes 0.0000132 AC: 2AN: 152072Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152072
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
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Gnomad SAS
AF:
Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000796 AC: 2AN: 251166 AF XY: 0.0000147 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
251166
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461842Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727228 show subpopulations
GnomAD4 exome
AF:
AC:
10
AN:
1461842
Hom.:
Cov.:
31
AF XY:
AC XY:
6
AN XY:
727228
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
1
AN:
86252
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
8
AN:
1111988
Other (OTH)
AF:
AC:
1
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.470
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000132 AC: 2AN: 152072Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74286 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152072
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74286
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41420
American (AMR)
AF:
AC:
0
AN:
15270
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5180
South Asian (SAS)
AF:
AC:
0
AN:
4818
European-Finnish (FIN)
AF:
AC:
0
AN:
10606
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
2
AN:
67990
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
AF:
AC:
2
ClinVar
ClinVar submissions
View on ClinVar Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
-
1
-
Inborn genetic diseases (1)
-
1
-
not provided (1)
-
-
1
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PhyloP100
PrimateAI
Benign
T
PROVEAN
Uncertain
N
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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