dbSNP rs201098465: CRTC2:p.Ser570Arg (chr1-153948609-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_181715.3(CRTC2):c.1710C>G(p.Ser570Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 1,596,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

CRTC2
NM_181715.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

Publications

3 publications found

Variant links:

Genes affected

CRTC2 (HGNC:27301): (CREB regulated transcription coactivator 2) This gene encodes a member of the transducers of regulated cAMP response element-binding protein activity family of transcription coactivators. These proteins promote the transcription of genes targeted by the cAMP response element-binding protein, and therefore play an important role in many cellular processes. Under basal conditions the encoded protein is phosphorylated by AMP-activated protein kinase or the salt-inducible kinases and is sequestered in the cytoplasm. Upon activation by elevated cAMP or calcium, the encoded protein translocates to the nucleus and increases target gene expression. Single nucleotide polymorphisms in this gene may increase the risk of type 2 diabetes. A pseudogene of this gene is located on the long arm of chromosome 5. [provided by RefSeq, Dec 2010]

CRTC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11900574).

BS2

High AC in GnomAd4 at 37 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181715.3. 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
	CRTC2	NM_181715.3	MANE Select	c.1710C>G	p.Ser570Arg	missense	Exon 13 of 14	NP_859066.1	Q53ET0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRTC2	ENST00000368633.2	TSL:1 MANE Select	c.1710C>G	p.Ser570Arg	missense	Exon 13 of 14	ENSP00000357622.1	Q53ET0
CRTC2	ENST00000461638.6	TSL:1	n.*91C>G		non_coding_transcript_exon	Exon 12 of 13	ENSP00000434115.2	H0YDQ8
CRTC2	ENST00000461638.6	TSL:1	n.*91C>G		3_prime_UTR	Exon 12 of 13	ENSP00000434115.2	H0YDQ8

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000182

AC:

AN:

230404

AF XY:

0.000216

show subpopulations

Gnomad AFR exome

AF:

0.0000627

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000975

Gnomad NFE exome

AF:

0.000360

Gnomad OTH exome

AF:

0.000181

GnomAD4 exome

AF:

0.000344

AC:

497

AN:

1443852

Hom.:

Cov.:

AF XY:

0.000351

AC XY:

252

AN XY:

717970

show subpopulations

African (AFR)

AF:

0.0000307

AC:

AN:

32526

American (AMR)

AF:

0.00

AC:

AN:

40826

Ashkenazi Jewish (ASJ)

AF:

0.0000407

AC:

AN:

24572

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

83522

European-Finnish (FIN)

AF:

0.0000379

AC:

AN:

52722

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5666

European-Non Finnish (NFE)

AF:

0.000437

AC:

483

AN:

1104876

Other (OTH)

AF:

0.000168

AC:

AN:

59498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

114

142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<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:

0.000243

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41570

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.000389

Hom.:

Bravo

AF:

0.000178

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

ClinVar submissions

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

Benign

0.30

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

Eigen

Benign

0.037

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.79

M_CAP

Benign

0.032

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.90

PhyloP100

1.7

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.047

Sift

Uncertain

0.0090

Sift4G

Benign

0.066

Polyphen

1.0

Vest4

0.44

MutPred

0.26

Loss of phosphorylation at S570 (P = 0.0156)

MVP

0.10

MPC

0.27

ClinPred

0.080

GERP RS

3.9

Varity_R

0.24

gMVP

0.56

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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