2-16588115-C-T

Variant names:

• chr2-16588115-C-T
• NM_030797.4:c.5G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_030797.4(CYRIA):​c.5G>A​(p.Gly2Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYRIA NM_030797.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.30
• Publications: 0 publications found

Genes affected

CYRIA (HGNC:25373): (CYFIP related Rac1 interactor A) Predicted to enable small GTPase binding activity. Predicted to be involved in regulation of actin filament polymerization. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030797.4. 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
	CYRIA	NM_030797.4	MANE Select	c.5G>A	p.Gly2Glu	missense	Exon 3 of 12	NP_110424.1	Q9H0Q0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYRIA	ENST00000381323.7	TSL:1 MANE Select	c.5G>A	p.Gly2Glu	missense	Exon 3 of 12	ENSP00000370724.3	Q9H0Q0
	CYRIA	ENST00000406434.5	TSL:5	c.5G>A	p.Gly2Glu	missense	Exon 4 of 13	ENSP00000384771.1	Q9H0Q0
	CYRIA	ENST00000871551.1		c.5G>A	p.Gly2Glu	missense	Exon 3 of 12	ENSP00000541610.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1452630 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 722570

African (AFR) AF: 0.00 AC: 0 AN: 33008

American (AMR) AF: 0.00 AC: 0 AN: 43704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25804

East Asian (EAS) AF: 0.00 AC: 0 AN: 39518

South Asian (SAS) AF: 0.00 AC: 0 AN: 84382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53146

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107402

Other (OTH) AF: 0.00 AC: 0 AN: 59956

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	-0.0045	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.3
PrimateAI	Pathogenic	0.93	D
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.94	P
Vest4		0.77
MutPred		0.60		Gain of helix (P = 0.062)
MVP		0.40
MPC		2.3
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.89
gMVP		0.95
Mutation Taster		=38/62	disease causing

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

hg19: chr2-16769383; COSMIC: COSV62864651;