2-225582004-A-G

Variant names:

• chr2-225582004-A-G
• rs1574691177
• NM_001371273.1:c.587A>G

Variant summary

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

The NM_001371273.1(NYAP2):​c.587A>G​(p.Lys196Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,461,388 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: NYAP2 NM_001371273.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.04

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.587A>G	p.Lys196Arg	missense_variant	Exon 5 of 8	ENST00000272907.8	NP_001358202.1
NYAP2	NM_020864.2	c.587A>G	p.Lys196Arg	missense_variant	Exon 4 of 6		NP_065915.1
NYAP2	XM_047445200.1	c.587A>G	p.Lys196Arg	missense_variant	Exon 5 of 8		XP_047301156.1
NYAP2	XM_047445201.1	c.587A>G	p.Lys196Arg	missense_variant	Exon 6 of 9		XP_047301157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NYAP2	ENST00000272907.8	c.587A>G	p.Lys196Arg	missense_variant	Exon 5 of 8	1	NM_001371273.1	ENSP00000272907.7
NYAP2	ENST00000636099.1	c.587A>G	p.Lys196Arg	missense_variant	Exon 5 of 7	5		ENSP00000490942.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461388 Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9 AN XY: 726908

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.587A>G (p.K196R) alteration is located in exon 4 (coding exon 3) of the NYAP2 gene. This alteration results from a A to G substitution at nucleotide position 587, causing the lysine (K) at amino acid position 196 to be replaced by an arginine (R). 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	0.095
BayesDel_addAF	Benign	-0.0048	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.8	.;N
REVEL	Benign	0.29
Sift	Benign	0.17	.;T
Sift4G	Benign	0.13	.;T
Polyphen		1.0	D;D
Vest4		0.66
MutPred		0.42		Loss of methylation at K196 (P = 0.0027);Loss of methylation at K196 (P = 0.0027);
MVP		0.15
MPC		0.98
ClinPred		0.94	D
GERP RS		5.9
Varity_R		0.18
gMVP		0.29

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: rs1574691177; hg19: chr2-226446720;