chr1-16451875-G-C

Position:

• chr1-16451875-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018090.5(NECAP2):​c.527G>C​(p.Arg176Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: NECAP2 NM_018090.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2885676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECAP2	NM_018090.5	c.527G>C	p.Arg176Pro	missense_variant	6/8	ENST00000337132.10	NP_060560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECAP2	ENST00000337132.10	c.527G>C	p.Arg176Pro	missense_variant	6/8	1	NM_018090.5	ENSP00000338746.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 30, 2024

The c.527G>C (p.R176P) alteration is located in exon 6 (coding exon 6) of the NECAP2 gene. This alteration results from a G to C substitution at nucleotide position 527, causing the arginine (R) at amino acid position 176 to be replaced by a proline (P). 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	Benign	0.30
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T;T;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	.;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	3.1	M;.;.;M
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Benign	0.093
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Benign	0.083	T;D;D;T
Polyphen		0.98	D;.;D;P
Vest4		0.43
MutPred		0.29		Loss of MoRF binding (P = 0.0075);.;.;Loss of MoRF binding (P = 0.0075);
MVP		0.61
MPC		0.49
ClinPred		0.98	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-16778370;