NM_001371273.1:c.587A>G

Variant names:

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

Variant summary

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

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
• 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 0 ACMG points.

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.587A>G	p.Lys196Arg	missense	Exon 5 of 8	NP_001358202.1	A0A8V8N5G5
	NYAP2	NM_020864.2		c.587A>G	p.Lys196Arg	missense	Exon 4 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.587A>G	p.Lys196Arg	missense	Exon 5 of 8	ENSP00000272907.7	A0A8V8N5G5
	NYAP2	ENST00000636099.1	TSL:5	c.587A>G	p.Lys196Arg	missense	Exon 5 of 7	ENSP00000490942.1	Q9P242-1

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

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111596

Other (OTH) AF: 0.00 AC: 0 AN: 60364

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	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
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
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.0
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
Vest4		0.66
MutPred		0.42		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
Mutation Taster		=39/61	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

dbSNP: rs1574691177; hg19: chr2-226446720;