2-225513375-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NYAP2	NM_001371273.1	c.226G>A	p.Gly76Ser	missense_variant	Exon 4 of 8	ENST00000272907.8	NP_001358202.1
NYAP2	NM_020864.2	c.226G>A	p.Gly76Ser	missense_variant	Exon 3 of 6		NP_065915.1
NYAP2	XM_047445200.1	c.226G>A	p.Gly76Ser	missense_variant	Exon 4 of 8		XP_047301156.1
NYAP2	XM_047445201.1	c.226G>A	p.Gly76Ser	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.226G>A	p.Gly76Ser	missense_variant	Exon 4 of 8	1	NM_001371273.1	ENSP00000272907.7
NYAP2	ENST00000636099.1	c.226G>A	p.Gly76Ser	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

May 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.226G>A (p.G76S) alteration is located in exon 3 (coding exon 2) of the NYAP2 gene. This alteration results from a G to A substitution at nucleotide position 226, causing the glycine (G) at amino acid position 76 to be replaced by a serine (S). 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	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;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;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L;L
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;D
Vest4		0.64
MutPred		0.24		Gain of phosphorylation at G76 (P = 0.0087);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

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

LitVar

Other links and lift over

dbSNP: rs911626600; hg19: chr2-226378091;