rs193921123

Positions:

• chr1-16449174-G-T

Variant summary

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

The NM_018090.5(NECAP2):​c.462G>T​(p.Glu154Asp) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NECAP2 NM_018090.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.827

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=0.3371086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECAP2	NM_018090.5	c.462G>T	p.Glu154Asp	missense_variant	5/8	ENST00000337132.10	NP_060560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECAP2	ENST00000337132.10	c.462G>T	p.Glu154Asp	missense_variant	5/8	1	NM_018090.5	ENSP00000338746.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;.;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	.;T;D;D
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M;.;.;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.5	D;N;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.025	D;D;D;T
Sift4G	Benign	0.085	T;D;D;D
Polyphen		0.12	B;.;B;B
Vest4		0.27
MutPred		0.57		Loss of ubiquitination at K153 (P = 0.0877);.;.;Loss of ubiquitination at K153 (P = 0.0877);
MVP		0.49
MPC		0.37
ClinPred		0.82	D
GERP RS		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.56

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

Other links and lift over

dbSNP: rs193921123; hg19: chr1-16775669; COSMIC: COSV61433743; COSMIC: COSV61433743;