chr1-16451875-G-C

Variant names:

• chr1-16451875-G-C
• NM_018090.5:c.527G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018090.5. 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
	NECAP2	NM_018090.5	MANE Select	c.527G>C	p.Arg176Pro	missense	Exon 6 of 8	NP_060560.1	Q9NVZ3-1
	NECAP2	NM_001145277.2		c.527G>C	p.Arg176Pro	missense	Exon 6 of 7	NP_001138749.1	Q9NVZ3-2
	NECAP2	NM_001145278.2		c.449G>C	p.Arg150Pro	missense	Exon 6 of 8	NP_001138750.1	Q9NVZ3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECAP2	ENST00000337132.10	TSL:1 MANE Select	c.527G>C	p.Arg176Pro	missense	Exon 6 of 8	ENSP00000338746.5	Q9NVZ3-1
	NECAP2	ENST00000443980.6	TSL:2	c.527G>C	p.Arg176Pro	missense	Exon 6 of 7	ENSP00000391942.2	Q9NVZ3-2
	NECAP2	ENST00000966887.1		c.527G>C	p.Arg176Pro	missense	Exon 6 of 8	ENSP00000636946.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		1.6
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.093
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.083	T
Polyphen		0.98	D
Vest4		0.43
MutPred		0.29		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
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

hg19: chr1-16778370;