2-225565341-T-G

Variant names:

• chr2-225565341-T-G
• rs1897227
• NM_001371273.1:c.524-16600T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371273.1(NYAP2):​c.524-16600T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,146 control chromosomes in the GnomAD database, including 976 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (976 hom., cov: 32)
• Consequence: NYAP2 NM_001371273.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NYAP2	NM_001371273.1	c.524-16600T>G		intron_variant	Intron 4 of 7	ENST00000272907.8	NP_001358202.1
NYAP2	NM_020864.2	c.524-16600T>G		intron_variant	Intron 3 of 5		NP_065915.1
NYAP2	XM_047445200.1	c.524-16600T>G		intron_variant	Intron 4 of 7		XP_047301156.1
NYAP2	XM_047445201.1	c.524-16600T>G		intron_variant	Intron 5 of 8		XP_047301157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NYAP2	ENST00000272907.8	c.524-16600T>G		intron_variant	Intron 4 of 7	1	NM_001371273.1	ENSP00000272907.7
NYAP2	ENST00000636099.1	c.524-16600T>G		intron_variant	Intron 4 of 6	5		ENSP00000490942.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16181 AN: 152028 Hom.: 975 Cov.: 32

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.0922

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0480

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.106

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.106 AC: 16183 AN: 152146 Hom.: 976 Cov.: 32 AF XY: 0.107 AC XY: 7959 AN XY: 74372

African (AFR) AF: 0.0643 AC: 2671 AN: 41538

American (AMR) AF: 0.0922 AC: 1407 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 394 AN: 3470

East Asian (EAS) AF: 0.0480 AC: 248 AN: 5172

South Asian (SAS) AF: 0.132 AC: 635 AN: 4822

European-Finnish (FIN) AF: 0.136 AC: 1442 AN: 10576

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8946 AN: 67988

Other (OTH) AF: 0.104 AC: 220 AN: 2114

Alfa AF: 0.115 Hom.: 1534

Bravo AF: 0.101

Asia WGS AF: 0.110 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.8
DANN	Benign	0.63
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs1897227; hg19: chr2-226430057;