rs200513983

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_080817.5(GPR82):c.876C>G(p.Asn292Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 112,175 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0000037 ( 0 hom. 3 hem. )

Failed GnomAD Quality Control

Consequence

GPR82
NM_080817.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.138

Publications

0 publications found

Variant links:

Genes affected

GPR82 (HGNC:4533): (G protein-coupled receptor 82) The protein encoded by this gene is an orphan G protein-coupled receptor of unknown function. The encoded protein is a member of a family of proteins that contain seven transmembrane domains and transduce extracellular signals through heterotrimeric G proteins. [provided by RefSeq, Sep 2011]

GPR82 links:

CASK (HGNC:1497): (calcium/calmodulin dependent serine protein kinase) This gene encodes a calcium/calmodulin-dependent serine protein kinase. The encoded protein is a MAGUK (membrane-associated guanylate kinase) protein family member. These proteins are scaffold proteins and the encoded protein is located at synapses in the brain. Mutations in this gene are associated with FG syndrome 4, intellectual disability and microcephaly with pontine and cerebellar hypoplasia, and a form of X-linked intellectual disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

CASK Gene-Disease associations (from GenCC):

FG syndrome 4
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
syndromic X-linked intellectual disability Najm type
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
X-linked syndromic intellectual disability
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CASK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080817.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR82	NM_080817.5	MANE Select	c.876C>G	p.Asn292Lys	missense	Exon 3 of 3	NP_543007.1	Q96P67
CASK	NM_001367721.1	MANE Select	c.429+11482G>C		intron	N/A	NP_001354650.1	O14936-1
CASK	NM_003688.4		c.429+11482G>C		intron	N/A	NP_003679.2	O14936-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR82	ENST00000302548.5	TSL:1 MANE Select	c.876C>G	p.Asn292Lys	missense	Exon 3 of 3	ENSP00000303549.4	Q96P67
CASK	ENST00000378163.7	TSL:5 MANE Select	c.429+11482G>C		intron	N/A	ENSP00000367405.1	O14936-1
CASK	ENST00000421587.8	TSL:1	c.447+11482G>C		intron	N/A	ENSP00000400526.4	A0A7I2RJN6

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112175

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000551

AC:

AN:

181489

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000367

AC:

AN:

1090448

Hom.:

Cov.:

AF XY:

0.00000842

AC XY:

AN XY:

356198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26243

American (AMR)

AF:

0.00

AC:

AN:

35094

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19322

East Asian (EAS)

AF:

0.00

AC:

AN:

30170

South Asian (SAS)

AF:

0.00

AC:

AN:

53733

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4116

European-Non Finnish (NFE)

AF:

0.00000479

AC:

AN:

835440

Other (OTH)

AF:

0.00

AC:

AN:

45822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000267

AC:

AN:

112175

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34345

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30918

American (AMR)

AF:

0.00

AC:

AN:

10556

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3613

South Asian (SAS)

AF:

0.00

AC:

AN:

2739

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6027

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000564

AC:

AN:

53226

Other (OTH)

AF:

0.00

AC:

AN:

1524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.049

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.75

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.97

PhyloP100

-0.14

PrimateAI

Uncertain

0.67

PROVEAN

Benign

0.69

REVEL

Benign

0.22

Sift

Benign

0.14

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.70

MutPred

0.66

Gain of ubiquitination at N292 (P = 0.0388)

MVP

0.42

MPC

0.77

ClinPred

0.41

GERP RS

-0.15

Varity_R

0.12

gMVP

0.55

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over