rs551248341

Variant names:

• chr1-153948215-C-G
• rs551248341
• NM_181715.3:c.1976G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-153948215-C-G
• chr1-153948215-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181715.3(CRTC2):​c.1976G>C​(p.Arg659Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,244 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R659H) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: CRTC2 NM_181715.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27037475).

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.1976G>C	p.Arg659Pro	missense	Exon 14 of 14	NP_859066.1	Q53ET0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRTC2	ENST00000368633.2	TSL:1 MANE Select	c.1976G>C	p.Arg659Pro	missense	Exon 14 of 14	ENSP00000357622.1	Q53ET0
	CRTC2	ENST00000461638.6	TSL:1	n.*357G>C		non_coding_transcript_exon	Exon 13 of 13	ENSP00000434115.2	H0YDQ8
	CRTC2	ENST00000461638.6	TSL:1	n.*357G>C		3_prime_UTR	Exon 13 of 13	ENSP00000434115.2	H0YDQ8

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152244 Hom.: 0 Cov.: 33

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152244 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.81	D
Eigen	Benign	-0.096
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.077
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.18
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.36		Loss of helix (P = 0.0237)
MVP		0.37
MPC		0.71
ClinPred		0.95	D
GERP RS		1.1
Varity_R		0.49
gMVP		0.66
Mutation Taster		=91/9	polymorphism

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: rs551248341; hg19: chr1-153920691;