Genetic Variant NYAP2:p.Gln21Glu (chr2-225408941-C-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001371273.1(NYAP2):c.61C>G(p.Gln21Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000462 in 1,611,804 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 0 hom. )

Consequence

NYAP2
NM_001371273.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.04

Publications

2 publications found

Variant links:

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]

NYAP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36743158).

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>G	p.Gln21Glu	missense	Exon 3 of 8	NP_001358202.1	A0A8V8N5G5
	NYAP2	NM_020864.2		c.61C>G	p.Gln21Glu	missense	Exon 2 of 6	NP_065915.1	Q9P242-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NYAP2	ENST00000272907.8	TSL:1 MANE Select	c.61C>G	p.Gln21Glu	missense	Exon 3 of 8	ENSP00000272907.7	A0A8V8N5G5
NYAP2	ENST00000636099.1	TSL:5	c.61C>G	p.Gln21Glu	missense	Exon 3 of 7	ENSP00000490942.1	Q9P242-1
NYAP2	ENST00000695958.1		n.681C>G		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes

AF:

0.000369

AC:

AN:

151922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000736

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.000366

AC:

AN:

248572

AF XY:

0.000349

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000756

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000471

AC:

688

AN:

1459882

Hom.:

Cov.:

AF XY:

0.000472

AC XY:

343

AN XY:

726290

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33392

American (AMR)

AF:

0.0000448

AC:

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.0000767

AC:

AN:

26064

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.00

AC:

AN:

86222

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000589

AC:

654

AN:

1110450

Other (OTH)

AF:

0.000365

AC:

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

130

162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000369

AC:

AN:

151922

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74196

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41384

American (AMR)

AF:

0.00

AC:

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000736

AC:

AN:

67972

Other (OTH)

AF:

0.000480

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000681

Hom.:

Bravo

AF:

0.000400

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000264

AC:

ESP6500EA

AF:

0.000727

AC:

ExAC

AF:

0.000463

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000474

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.70

M_CAP

Benign

0.018

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.4

PhyloP100

7.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.36

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.011

Polyphen

0.99

Vest4

0.94

MVP

0.25

MPC

1.1

ClinPred

0.46

GERP RS

5.9

Varity_R

0.23

gMVP

0.46

Mutation Taster

=64/36

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over