Variant chr1-16440774-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018090.5(NECAP2):c.13G>C(p.Gly5Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000489 in 1,614,080 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 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 1 hom. )

Consequence

NECAP2
NM_018090.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

NECAP2 (HGNC:):

NECAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03791803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECAP2	NM_018090.5 linkuse as main transcript	c.13G>C	p.Gly5Arg	missense_variant	1/8	ENST00000337132.10	NP_060560.1	Q9NVZ3-1
NECAP2	NM_001145277.2 linkuse as main transcript	c.13G>C	p.Gly5Arg	missense_variant	1/7		NP_001138749.1	Q9NVZ3-2
NECAP2	XM_047424715.1 linkuse as main transcript	c.13G>C	p.Gly5Arg	missense_variant	1/7		XP_047280671.1
NECAP2	NM_001145278.2 linkuse as main transcript	c.13G>C	p.Gly5Arg	missense_variant, splice_region_variant	1/8		NP_001138750.1	Q9NVZ3-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECAP2	ENST00000337132.10 linkuse as main transcript	c.13G>C	p.Gly5Arg	missense_variant	1/8	1	NM_018090.5	ENSP00000338746.5		Q9NVZ3-1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000478

GnomAD3 exomes

AF:

0.0000836

AC:

AN:

251062

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1461742

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000256

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.000196

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:

0.000473

Bravo

AF:

0.000298

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.13G>C (p.G5R) alteration is located in exon 1 (coding exon 1) of the NECAP2 gene. This alteration results from a G to C substitution at nucleotide position 13, causing the glycine (G) at amino acid position 5 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0073

T;T;.;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.46

LIST_S2

Uncertain

0.88

.;D;T;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.030

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

0.064

Sift

Uncertain

0.023

D;D;T;T

Sift4G

Benign

0.38

T;T;T;T

Polyphen

0.060

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

0.10

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)

0.0

Details are displayed if max score is > 0.2

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

Publications

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over