Variant 5-43039871-C-T 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.176G>A(p.Ser59Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,890 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000027 ( 1 hom. )

Consequence

ANXA2R
NM_001014279.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.132

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=0.07211861).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ANXA2R	NM_001014279.3 linkuse as main transcript	c.176G>A	p.Ser59Asn	missense_variant	1/1	ENST00000616064.2	NP_001014301.1
ANXA2R-OT1	NR_104651.1 linkuse as main transcript	n.214-24721G>A		intron_variant, non_coding_transcript_variant
ANXA2R	NM_001382352.1 linkuse as main transcript	c.176G>A	p.Ser59Asn	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.176G>A	p.Ser59Asn	missense_variant	1/1		NM_001014279.3	ENSP00000479862	P1
ANXA2R-OT1	ENST00000503152.2 linkuse as main transcript	n.227-24721G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251434

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

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:

0.00000274

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

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

Dec 08, 2023

The c.176G>A (p.S59N) alteration is located in exon 1 (coding exon 1) of the ANXA2R gene. This alteration results from a G to A substitution at nucleotide position 176, causing the serine (S) at amino acid position 59 to be replaced by an asparagine (N). 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

0.42

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.54

DEOGEN2

Benign

0.0016

T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.25

T;.

M_CAP

Benign

0.0032

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.68

.;N

REVEL

Benign

0.061

Sift

Benign

0.93

.;T

Sift4G

Benign

0.46

T;T

Polyphen

0.98

D;D

Vest4

0.18

MutPred

0.23

Loss of disorder (P = 0.0926);Loss of disorder (P = 0.0926);

MVP

0.12

MPC

0.36

ClinPred

0.068

GERP RS

1.6

Varity_R

0.046

gMVP

0.017

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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