2-16559549-T-C

Variant names:

• chr2-16559549-T-C
• NM_030797.4:c.748A>G

Variant summary

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

The NM_030797.4(CYRIA):​c.748A>G​(p.Met250Val) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYRIA NM_030797.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.692
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15961769).

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.748A>G	p.Met250Val	missense	Exon 10 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.748A>G	p.Met250Val	missense	Exon 10 of 12	ENSP00000370724.3	Q9H0Q0
	CYRIA	ENST00000406434.5	TSL:5	c.748A>G	p.Met250Val	missense	Exon 11 of 13	ENSP00000384771.1	Q9H0Q0
	CYRIA	ENST00000871551.1		c.748A>G	p.Met250Val	missense	Exon 10 of 12	ENSP00000541610.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.69
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.082
Sift	Benign	0.11	T
Sift4G	Benign	0.32	T
Polyphen		0.0090	B
Vest4		0.47
MutPred		0.55		Loss of catalytic residue at M250 (P = 0.0862)
MVP		0.068
MPC		1.0
ClinPred		0.090	T
GERP RS		1.2
Varity_R		0.12
gMVP		0.53
Mutation Taster		=97/3	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

hg19: chr2-16740817;