NM_001371273.1:c.272A>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NYAP2	NM_001371273.1	c.272A>C	p.His91Pro	missense_variant	Exon 4 of 8	ENST00000272907.8	NP_001358202.1
NYAP2	NM_020864.2	c.272A>C	p.His91Pro	missense_variant	Exon 3 of 6		NP_065915.1
NYAP2	XM_047445200.1	c.272A>C	p.His91Pro	missense_variant	Exon 4 of 8		XP_047301156.1
NYAP2	XM_047445201.1	c.272A>C	p.His91Pro	missense_variant	Exon 5 of 9		XP_047301157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NYAP2	ENST00000272907.8	c.272A>C	p.His91Pro	missense_variant	Exon 4 of 8	1	NM_001371273.1	ENSP00000272907.7
NYAP2	ENST00000636099.1	c.272A>C	p.His91Pro	missense_variant	Exon 4 of 7	5		ENSP00000490942.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.272A>C (p.H91P) alteration is located in exon 3 (coding exon 2) of the NYAP2 gene. This alteration results from a A to C substitution at nucleotide position 272, causing the histidine (H) at amino acid position 91 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;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;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.7	M;M
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;D
Vest4		0.97
MutPred		0.46		Gain of loop (P = 0.0079);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-226378137;