Variant 2-196989644-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001195144.2(ANKRD44):c.2929A>G(p.Arg977Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000158 in 1,550,320 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: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ANKRD44
NM_001195144.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

Variant links:

Genes affected

ANKRD44 (HGNC:25259): (ankyrin repeat domain 44)

ANKRD44 links:

ANKRD44 (HGNC:):

ANKRD44 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02558291).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD44	NM_001195144.2 linkuse as main transcript	c.2929A>G	p.Arg977Gly	missense_variant	28/28	ENST00000282272.15	NP_001182073.1	Q8N8A2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANKRD44	ENST00000282272.15 linkuse as main transcript	c.2929A>G	p.Arg977Gly	missense_variant	28/28	5	NM_001195144.2	ENSP00000282272.9	Q8N8A2-1
ANKRD44	ENST00000424317.5 linkuse as main transcript	c.2368+3939A>G		intron_variant		1		ENSP00000403415.1	H7C209
ANKRD44	ENST00000647377 linkuse as main transcript	c.*1036A>G		3_prime_UTR_variant	28/28			ENSP00000496628.1	A0A2R8Y7Y4

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000201

AC:

AN:

149170

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

80360

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000488

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000577

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000727

Gnomad OTH exome

AF:

0.000232

GnomAD4 exome

AF:

0.000143

AC:

200

AN:

1397972

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

127

AN XY:

689528

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000364

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000808

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000927

Gnomad4 OTH exome

AF:

0.000311

GnomAD4 genome

AF:

0.000295

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000197

Hom.:

Bravo

AF:

0.000261

ExAC

AF:

0.000411

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

Oct 30, 2023

The c.2929A>G (p.R977G) alteration is located in exon 28 (coding exon 28) of the ANKRD44 gene. This alteration results from a A to G substitution at nucleotide position 2929, causing the arginine (R) at amino acid position 977 to be replaced by a glycine (G). 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

0.089

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0061

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.80

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.56

REVEL

Benign

0.25

Sift4G

Uncertain

0.037

Vest4

0.51

MVP

0.59

ClinPred

0.11

GERP RS

6.1

Varity_R

0.28

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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