2-225408941-C-T

Variant names:

• chr2-225408941-C-T
• rs201512658
• NM_001371273.1:c.61C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001371273.1(NYAP2):​c.61C>T​(p.Gln21*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000685 in 1,459,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NYAP2 NM_001371273.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

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

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.61C>T	p.Gln21*	stop_gained	Exon 3 of 8	NP_001358202.1	A0A8V8N5G5
	NYAP2	NM_020864.2		c.61C>T	p.Gln21*	stop_gained	Exon 2 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.61C>T	p.Gln21*	stop_gained	Exon 3 of 8	ENSP00000272907.7	A0A8V8N5G5
	NYAP2	ENST00000636099.1	TSL:5	c.61C>T	p.Gln21*	stop_gained	Exon 3 of 7	ENSP00000490942.1	Q9P242-1
	NYAP2	ENST00000695958.1		n.681C>T		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459886 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726292

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110454

Other (OTH) AF: 0.00 AC: 0 AN: 60282

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.66
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.1
FATHMM_MKL	Pathogenic	0.98	D
PhyloP100		7.0
Vest4		0.31
GERP RS		5.9
Mutation Taster		=2/198	disease causing (fs/PTC)

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: rs201512658; hg19: chr2-226273657; COSMIC: COSV107252952;