rs2904524

Variant names:

• chr12-70296305-G-A
• rs2904524
• NM_014515.7:c.49-14590G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-70296305-G-A
• chr12-70296305-G-C
• chr12-70296305-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014515.7(CNOT2):​c.49-14590G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,094 control chromosomes in the GnomAD database, including 2,155 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2155 hom., cov: 31)
• Consequence: CNOT2 NM_014515.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157
• Publications: 8 publications found

Genes affected

CNOT2 (HGNC:7878): (CCR4-NOT transcription complex subunit 2) This gene encodes a subunit of the multi-component CCR4-NOT complex. The CCR4-NOT complex regulates mRNA synthesis and degradation and is also thought to be involved in mRNA splicing, transport and localization. The encoded protein interacts with histone deacetylases and functions as a repressor of polymerase II transcription. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

CNOT2 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNOT2	NM_014515.7	c.49-14590G>A		intron_variant	Intron 2 of 15	ENST00000229195.8	NP_055330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT2	ENST00000229195.8	c.49-14590G>A		intron_variant	Intron 2 of 15	1	NM_014515.7	ENSP00000229195.3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23936 AN: 151976 Hom.: 2151 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.158 AC: 23979 AN: 152094 Hom.: 2155 Cov.: 31 AF XY: 0.161 AC XY: 12005 AN XY: 74340

African (AFR) AF: 0.137 AC: 5694 AN: 41522

American (AMR) AF: 0.282 AC: 4310 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3472

East Asian (EAS) AF: 0.225 AC: 1160 AN: 5164

South Asian (SAS) AF: 0.184 AC: 891 AN: 4832

European-Finnish (FIN) AF: 0.209 AC: 2214 AN: 10570

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8796 AN: 67958

Other (OTH) AF: 0.171 AC: 360 AN: 2110

Alfa AF: 0.133 Hom.: 1719

Bravo AF: 0.166

Asia WGS AF: 0.267 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.63
PhyloP100		-0.16
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

Other links and lift over

dbSNP: rs2904524; hg19: chr12-70690085;