Variant 5-73555505-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_023039.5(ANKRA2):c.595G>C(p.Glu199Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ANKRA2
NM_023039.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.82

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:

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ACMG classification

Classification made for transcript

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=0.40982634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ANKRA2	NM_023039.5 linkuse as main transcript	c.595G>C	p.Glu199Gln	missense_variant	5/9	ENST00000296785.8	NP_075526.1
ANKRA2	XM_005248560.4 linkuse as main transcript	c.391G>C	p.Glu131Gln	missense_variant	5/9		XP_005248617.1
ANKRA2	XM_017009678.3 linkuse as main transcript	c.112G>C	p.Glu38Gln	missense_variant	4/8		XP_016865167.1
ANKRA2	XM_047417455.1 linkuse as main transcript	c.*86G>C		3_prime_UTR_variant	6/6		XP_047273411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRA2	ENST00000296785.8 linkuse as main transcript	c.595G>C	p.Glu199Gln	missense_variant	5/9	1	NM_023039.5	ENSP00000296785	P1
ANKRA2	ENST00000504641.1 linkuse as main transcript	c.436G>C	p.Glu146Gln	missense_variant	4/5	3		ENSP00000422643

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251378

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461234

Hom.:

Cov.:

AF XY:

0.00000138

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:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000848

Hom.:

Bravo

AF:

0.00000756

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

Aug 30, 2022

The c.595G>C (p.E199Q) alteration is located in exon 5 (coding exon 4) of the ANKRA2 gene. This alteration results from a G to C substitution at nucleotide position 595, causing the glutamic acid (E) at amino acid position 199 to be replaced by a glutamine (Q). 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

0.54

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

T;T

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.41

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

0.43

N;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.18

N;N

REVEL

Benign

0.27

Sift

Benign

0.35

T;T

Sift4G

Benign

0.21

T;.

Polyphen

0.98

D;.

Vest4

0.59

MVP

0.86

MPC

0.45

ClinPred

0.34

GERP RS

5.6

Varity_R

0.29

gMVP

0.45

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

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