Variant 5-73554977-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_023039.5(ANKRA2):c.622C>A(p.Pro208Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,770 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 7.66

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ANKRA2	NM_023039.5 linkuse as main transcript	c.622C>A	p.Pro208Thr	missense_variant	6/9	ENST00000296785.8	NP_075526.1
ANKRA2	XM_005248560.4 linkuse as main transcript	c.418C>A	p.Pro140Thr	missense_variant	6/9		XP_005248617.1
ANKRA2	XM_017009678.3 linkuse as main transcript	c.139C>A	p.Pro47Thr	missense_variant	5/8		XP_016865167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ANKRA2	ENST00000296785.8 linkuse as main transcript	c.622C>A	p.Pro208Thr	missense_variant	6/9	1	NM_023039.5	ENSP00000296785	P1
ANKRA2	ENST00000504641.1 linkuse as main transcript	c.463C>A	p.Pro155Thr	missense_variant	5/5	3		ENSP00000422643
ANKRA2	ENST00000515249.1 linkuse as main transcript	n.232C>A		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460770

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726652

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:

0.00000180

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

Dec 11, 2023

The c.622C>A (p.P208T) alteration is located in exon 6 (coding exon 5) of the ANKRA2 gene. This alteration results from a C to A substitution at nucleotide position 622, causing the proline (P) at amino acid position 208 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

Uncertain

0.52

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Benign

-0.37

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-4.0

D;D

REVEL

Uncertain

0.48

Sift

Benign

0.31

T;T

Sift4G

Benign

0.27

T;.

Polyphen

1.0

D;.

Vest4

0.68

MutPred

0.44

Loss of disorder (P = 0.1053);.;

MVP

0.82

MPC

0.51

ClinPred

0.92

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.73

gMVP

0.72

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