Variant 5-73562710-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000296785.8(ANKRA2):c.172A>G(p.Asn58Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,252 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Consequence

ANKRA2
ENST00000296785.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63

Variant links:

Genes affected

ANKRA2 (HGNC:13208): (ankyrin repeat family A member 2) Enables enzyme binding activity and low-density lipoprotein particle receptor binding activity. Involved in regulation of protein-containing complex assembly. Located in cytosol and membrane. Part of protein-containing complex. Colocalizes with 3M complex. [provided by Alliance of Genome Resources, Apr 2022]

ANKRA2 links:

ANKRA2 (HGNC:):

ANKRA2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRA2	NM_023039.5 linkuse as main transcript	c.172A>G	p.Asn58Asp	missense_variant	2/9	ENST00000296785.8	NP_075526.1	Q9H9E1A0A024RAN7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANKRA2	ENST00000296785.8 linkuse as main transcript	c.172A>G	p.Asn58Asp	missense_variant	2/9	1	NM_023039.5	ENSP00000296785.3	Q9H9E1
ANKRA2	ENST00000504641.1 linkuse as main transcript	c.172A>G	p.Asn58Asp	missense_variant	2/5	3		ENSP00000422643.1	D6RBK8
ANKRA2	ENST00000509433.1 linkuse as main transcript	n.349A>G		non_coding_transcript_exon_variant	2/2	2
ANKRA2	ENST00000515804.1 linkuse as main transcript	n.812A>G		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

May 09, 2023

The c.172A>G (p.N58D) alteration is located in exon 2 (coding exon 1) of the ANKRA2 gene. This alteration results from a A to G substitution at nucleotide position 172, causing the asparagine (N) at amino acid position 58 to be replaced by an aspartic acid (D). 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

0.44

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.50

T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.050

N;N

REVEL

Benign

0.22

Sift

Uncertain

0.012

D;T

Sift4G

Uncertain

0.028

D;.

Polyphen

0.96

P;D

Vest4

0.82

MutPred

0.44

Loss of MoRF binding (P = 0.0683);Loss of MoRF binding (P = 0.0683);

MVP

0.64

MPC

1.0

ClinPred

0.90

GERP RS

5.2

Varity_R

0.28

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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