dbSNP rs145414698: NECAP2:p.Gly5Arg (chr1-16440774-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_018090.5(NECAP2):c.13G>A(p.Gly5Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NECAP2
NM_018090.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.36

Variant links:

Genes affected

NECAP2 (HGNC:25528): (NECAP endocytosis associated 2) This gene likely encodes a member of the adaptin-ear-binding coat-associated protein family. Studies of a similar protein in rat suggest a role in clathrin-mediated endocytosis. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

NECAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
NECAP2	NM_018090.5 link	c.13G>A	p.Gly5Arg	missense_variant	Exon 1 of 8	ENST00000337132.10	NP_060560.1	Q9NVZ3-1
NECAP2	NM_001145277.2 link	c.13G>A	p.Gly5Arg	missense_variant	Exon 1 of 7		NP_001138749.1	Q9NVZ3-2
NECAP2	XM_047424715.1 link	c.13G>A	p.Gly5Arg	missense_variant	Exon 1 of 7		XP_047280671.1
NECAP2	NM_001145278.2 link	c.13G>A	p.Gly5Arg	missense_variant, splice_region_variant	Exon 1 of 8		NP_001138750.1	Q9NVZ3-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECAP2	ENST00000337132.10 link	c.13G>A	p.Gly5Arg	missense_variant	Exon 1 of 8	1	NM_018090.5	ENSP00000338746.5		Q9NVZ3-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461742

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0073

T;T;.;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.28

LIST_S2

Uncertain

0.88

.;D;T;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.19

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.;L;L

PrimateAI

Benign

0.44

PROVEAN

Benign

0.49

N;N;N;N

REVEL

Benign

0.078

Sift

Uncertain

0.023

D;D;T;T

Sift4G

Benign

0.38

T;T;T;T

Polyphen

0.12

B;.;B;B

Vest4

0.17

MutPred

0.41

Loss of glycosylation at S4 (P = 0.0405);Loss of glycosylation at S4 (P = 0.0405);Loss of glycosylation at S4 (P = 0.0405);Loss of glycosylation at S4 (P = 0.0405);

MVP

0.42

MPC

0.44

ClinPred

0.77

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.40

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.39

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.39

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over