Variant 5-43039551-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001014279.3(ANXA2R):c.496C>G(p.Leu166Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ANXA2R
NM_001014279.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.439

Variant links:

Genes affected

ANXA2R (HGNC:33463): (annexin A2 receptor) Predicted to enable signaling receptor activity. [provided by Alliance of Genome Resources, Apr 2022]

ANXA2R links:

ANXA2R-OT1 (HGNC:48996): (ANXA2R overlapping transcript 1)

ANXA2R-OT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12379667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ANXA2R	NM_001014279.3 linkuse as main transcript	c.496C>G	p.Leu166Val	missense_variant	1/1	ENST00000616064.2	NP_001014301.1
ANXA2R-OT1	NR_104651.1 linkuse as main transcript	n.214-24401C>G		intron_variant, non_coding_transcript_variant
ANXA2R	NM_001382352.1 linkuse as main transcript	c.496C>G	p.Leu166Val	missense_variant	2/2		NP_001369281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA2R	ENST00000616064.2 linkuse as main transcript	c.496C>G	p.Leu166Val	missense_variant	1/1		NM_001014279.3	ENSP00000479862	P1
ANXA2R-OT1	ENST00000503152.2 linkuse as main transcript	n.227-24401C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461432

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 17, 2023

The c.496C>G (p.L166V) alteration is located in exon 1 (coding exon 1) of the ANXA2R gene. This alteration results from a C to G substitution at nucleotide position 496, causing the leucine (L) at amino acid position 166 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.2

DANN

Benign

0.88

DEOGEN2

Benign

0.0042

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.37

T;.

M_CAP

Benign

0.012

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.96

.;N

REVEL

Benign

0.036

Sift

Pathogenic

0.0

.;D

Sift4G

Benign

0.096

T;T

Polyphen

0.99

D;D

Vest4

0.19

MutPred

0.26

Loss of catalytic residue at L166 (P = 0.0016);Loss of catalytic residue at L166 (P = 0.0016);

MVP

0.15

MPC

1.0

ClinPred

0.23

GERP RS

-2.6

Varity_R

0.21

gMVP

0.0079

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over