chr5-73562737-C-T

Position:

chr5-73562737-C-T

Variant summary

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

The ENST00000296785.8(ANKRA2):c.145G>A(p.Ala49Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ANKRA2
ENST00000296785.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.45

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:

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=0.13198167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRA2	NM_023039.5 linkuse as main transcript	c.145G>A	p.Ala49Thr	missense_variant	2/9	ENST00000296785.8	NP_075526.1	Q9H9E1A0A024RAN7
ANKRA2	XM_047417455.1 linkuse as main transcript	c.145G>A	p.Ala49Thr	missense_variant	2/6		XP_047273411.1
ANKRA2	XM_005248560.4 linkuse as main transcript	c.-73G>A		5_prime_UTR_variant	2/9		XP_005248617.1
ANKRA2	XM_017009678.3 linkuse as main transcript	c.-195+17G>A		intron_variant			XP_016865167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANKRA2	ENST00000296785.8 linkuse as main transcript	c.145G>A	p.Ala49Thr	missense_variant	2/9	1	NM_023039.5	ENSP00000296785.3	Q9H9E1
ANKRA2	ENST00000504641.1 linkuse as main transcript	c.145G>A	p.Ala49Thr	missense_variant	2/5	3		ENSP00000422643.1	D6RBK8
ANKRA2	ENST00000509433.1 linkuse as main transcript	n.322G>A		non_coding_transcript_exon_variant	2/2	2
ANKRA2	ENST00000515804.1 linkuse as main transcript	n.785G>A		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251474

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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:

0.00000137

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

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

Nov 13, 2023

The c.145G>A (p.A49T) alteration is located in exon 2 (coding exon 1) of the ANKRA2 gene. This alteration results from a G to A substitution at nucleotide position 145, causing the alanine (A) at amino acid position 49 to be replaced by a threonine (T). 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

0.083

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.072

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.29

N;N

REVEL

Benign

0.23

Sift

Benign

0.040

D;D

Sift4G

Uncertain

0.0090

D;.

Polyphen

0.0

B;B

Vest4

0.42

MutPred

0.29

Loss of catalytic residue at A49 (P = 0.1059);Loss of catalytic residue at A49 (P = 0.1059);

MVP

0.64

MPC

0.27

ClinPred

0.51

GERP RS

3.4

Varity_R

0.071

gMVP

0.54

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