1-154602564-C-G

Variant names:

• chr1-154602564-C-G
• rs1802645
• NM_001111.5:c.78G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001111.5(ADAR):​c.78G>C​(p.Arg26Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R26R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ADAR NM_001111.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• Publications: 18 publications found

Genes affected

ADAR (HGNC:225): (adenosine deaminase RNA specific) This gene encodes the enzyme responsible for RNA editing by site-specific deamination of adenosines. This enzyme destabilizes double-stranded RNA through conversion of adenosine to inosine. Mutations in this gene have been associated with dyschromatosis symmetrica hereditaria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

ADAR Gene-Disease associations (from GenCC):

• Aicardi-Goutieres syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• dyschromatosis symmetrica hereditaria

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• Aicardi-Goutieres syndrome 6

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• familial infantile bilateral striatal necrosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18575099).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001111.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	NM_001111.5	MANE Select	c.78G>C	p.Arg26Ser	missense	Exon 2 of 15	NP_001102.3
	ADAR	NM_001365045.1		c.105G>C	p.Arg35Ser	missense	Exon 2 of 15	NP_001351974.1
	ADAR	NM_015840.4		c.78G>C	p.Arg26Ser	missense	Exon 2 of 15	NP_056655.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAR	ENST00000368474.9	TSL:1 MANE Select	c.78G>C	p.Arg26Ser	missense	Exon 2 of 15	ENSP00000357459.4
	ADAR	ENST00000368471.8	TSL:1	c.-808G>C		5_prime_UTR	Exon 2 of 15	ENSP00000357456.3
	ADAR	ENST00000649724.2		c.108G>C	p.Arg36Ser	missense	Exon 2 of 15	ENSP00000497932.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 42629

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.6
DANN	Benign	0.94
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.38
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.033
Sift	Benign	0.041	D
Sift4G	Benign	0.19	T
Polyphen		0.0060	B
Vest4		0.078
MutPred		0.29		Gain of phosphorylation at R26 (P = 0.0471)
MVP		0.30
MPC		0.37
ClinPred		0.21	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.077
gMVP		0.24
Mutation Taster		=283/17	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: rs1802645; hg19: chr1-154575040;