Variant 2-197001769-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001195144.2(ANKRD44):c.2419C>T(p.Pro807Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,306 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ANKRD44
NM_001195144.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.92

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 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
ANKRD44	NM_001195144.2 linkuse as main transcript	c.2419C>T	p.Pro807Ser	missense_variant	22/28	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.2419C>T	p.Pro807Ser	missense_variant	22/28	5	NM_001195144.2	ENSP00000282272.9	Q8N8A2-1
ANKRD44	ENST00000424317.5 linkuse as main transcript	c.1864C>T	p.Pro622Ser	missense_variant	16/22	1		ENSP00000403415.1	H7C209
ANKRD44	ENST00000647377.1 linkuse as main transcript	c.2419C>T	p.Pro807Ser	missense_variant	22/28			ENSP00000496628.1	A0A2R8Y7Y4
ANKRD44	ENST00000328737.6 linkuse as main transcript	c.2344C>T	p.Pro782Ser	missense_variant	22/26	2		ENSP00000331516.2	Q8N8A2-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251238

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460306

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726540

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:

0.00

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

Sep 25, 2024

The c.2419C>T (p.P807S) alteration is located in exon 22 (coding exon 22) of the ANKRD44 gene. This alteration results from a C to T substitution at nucleotide position 2419, causing the proline (P) at amino acid position 807 to be replaced by a serine (S). 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

Pathogenic

0.84

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

.;.;T;.

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

1.0

D;D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.70

D;D;D;D

MetaSVM

Uncertain

0.17

MutationAssessor

Uncertain

2.8

.;.;M;.

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-5.3

D;.;.;D

REVEL

Uncertain

0.54

Sift

Uncertain

0.0030

D;.;.;D

Sift4G

Benign

0.073

T;.;T;T

Vest4

0.70, 0.78

MVP

0.75

ClinPred

0.99

GERP RS

5.2

Varity_R

0.56

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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