chr2-225513421-A-C

Variant names:

• chr2-225513421-A-C
• NM_001371273.1:c.272A>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001371273.1(NYAP2):​c.272A>C​(p.His91Pro) 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)
• Consequence: NYAP2 NM_001371273.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.88
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.82

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.272A>C	p.His91Pro	missense	Exon 4 of 8	NP_001358202.1	A0A8V8N5G5
	NYAP2	NM_020864.2		c.272A>C	p.His91Pro	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.272A>C	p.His91Pro	missense	Exon 4 of 8	ENSP00000272907.7	A0A8V8N5G5
	NYAP2	ENST00000636099.1	TSL:5	c.272A>C	p.His91Pro	missense	Exon 4 of 7	ENSP00000490942.1	Q9P242-1

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	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.083	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		8.9
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.018	D
Polyphen		0.99	D
Vest4		0.97
MutPred		0.46		Gain of loop (P = 0.0079)
MVP		0.37
MPC		1.2
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.80
gMVP		0.59
Mutation Taster		=19/81	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: chr2-226378137;