chr2-225513375-G-A

Variant names:

• chr2-225513375-G-A
• rs911626600
• NM_001371273.1:c.226G>A

Variant summary

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

The NM_001371273.1(NYAP2):​c.226G>A​(p.Gly76Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NYAP2 NM_001371273.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.53
• Publications: 0 publications found

Genes affected

NYAP2 (HGNC:29291): (neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adaptor 2) Predicted to be involved in neuron projection morphogenesis and phosphatidylinositol 3-kinase signaling. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371273.1. 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
	NYAP2	NM_001371273.1	MANE Select	c.226G>A	p.Gly76Ser	missense	Exon 4 of 8	NP_001358202.1	A0A8V8N5G5
	NYAP2	NM_020864.2		c.226G>A	p.Gly76Ser	missense	Exon 3 of 6	NP_065915.1	Q9P242-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NYAP2	ENST00000272907.8	TSL:1 MANE Select	c.226G>A	p.Gly76Ser	missense	Exon 4 of 8	ENSP00000272907.7	A0A8V8N5G5
	NYAP2	ENST00000636099.1	TSL:5	c.226G>A	p.Gly76Ser	missense	Exon 4 of 7	ENSP00000490942.1	Q9P242-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.13
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0091	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L
PhyloP100		9.5
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.22
Sift	Benign	0.62	T
Sift4G	Benign	0.47	T
Polyphen		1.0	D
Vest4		0.64
MutPred		0.24		Gain of phosphorylation at G76 (P = 0.0087)
MVP		0.10
MPC		0.37
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.21
gMVP		0.33
Mutation Taster		=31/69	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

dbSNP: rs911626600; hg19: chr2-226378091;