2-225409058-G-A

Variant names:

• chr2-225409058-G-A
• NM_001371273.1:c.178G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001371273.1(NYAP2):​c.178G>A​(p.Glu60Lys) 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: 8.93

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.178G>A	p.Glu60Lys	missense_variant	Exon 3 of 8	ENST00000272907.8	NP_001358202.1
NYAP2	NM_020864.2	c.178G>A	p.Glu60Lys	missense_variant	Exon 2 of 6		NP_065915.1
NYAP2	XM_047445200.1	c.178G>A	p.Glu60Lys	missense_variant	Exon 3 of 8		XP_047301156.1
NYAP2	XM_047445201.1	c.178G>A	p.Glu60Lys	missense_variant	Exon 4 of 9		XP_047301157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NYAP2	ENST00000272907.8	c.178G>A	p.Glu60Lys	missense_variant	Exon 3 of 8	1	NM_001371273.1	ENSP00000272907.7
NYAP2	ENST00000636099.1	c.178G>A	p.Glu60Lys	missense_variant	Exon 3 of 7	5		ENSP00000490942.1
NYAP2	ENST00000695958.1	n.798G>A		non_coding_transcript_exon_variant	Exon 3 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 14, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.178G>A (p.E60K) alteration is located in exon 2 (coding exon 1) of the NYAP2 gene. This alteration results from a G to A substitution at nucleotide position 178, causing the glutamic acid (E) at amino acid position 60 to be replaced by a lysine (K). 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	0.89
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	T;T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.6	.;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.013	.;D
Sift4G	Benign	0.28	.;T
Polyphen		1.0	D;D
Vest4		0.80
MutPred		0.24		Gain of MoRF binding (P = 0.0132);Gain of MoRF binding (P = 0.0132);
MVP		0.068
MPC		1.1
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.51
gMVP		0.70

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: chr2-226273774;