Variant 2-97194844-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_001354587.1(ANKRD36):c.2479-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000594 in 1,591,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 45)

Exomes 𝑓: 0.00058 ( 0 hom. )

Consequence

ANKRD36
NM_001354587.1 splice_acceptor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.30

Variant links:

Genes affected

ANKRD36 (HGNC:24079): (ankyrin repeat domain 36)

ANKRD36 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 2-97194844-G-A is Pathogenic according to our data. Variant chr2-97194844-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 917512.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD36	NM_001354587.1 link	c.2479-1G>A		splice_acceptor_variant, intron_variant	Intron 39 of 75	ENST00000420699.9	NP_001341516.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANKRD36	ENST00000420699.9 link	c.2479-1G>A	splice_acceptor_variant, intron_variant	Intron 39 of 75	5	NM_001354587.1	ENSP00000391950.4	A6QL64-1
ANKRD36	ENST00000461153.7 link	c.2479-1G>A	splice_acceptor_variant, intron_variant	Intron 39 of 74	5		ENSP00000419530.3	A6QL64-1
ANKRD36	ENST00000652721.1 link	c.2479-1G>A	splice_acceptor_variant, intron_variant	Intron 39 of 75			ENSP00000498611.1	A6QL64-1

Frequencies

GnomAD3 genomes

AF:

0.000744

AC:

113

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000985

Gnomad ASJ

AF:

0.0194

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00118

AC:

258

AN:

218424

Hom.:

AF XY:

0.00112

AC XY:

133

AN XY:

118696

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000950

Gnomad ASJ exome

AF:

0.0193

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000220

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000358

Gnomad OTH exome

AF:

0.000717

GnomAD4 exome

AF:

0.000579

AC:

834

AN:

1439462

Hom.:

Cov.:

AF XY:

0.000589

AC XY:

421

AN XY:

715168

show subpopulations

Gnomad4 AFR exome

AF:

0.0000608

Gnomad4 AMR exome

AF:

0.000844

Gnomad4 ASJ exome

AF:

0.0181

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000335

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000178

Gnomad4 OTH exome

AF:

0.00164

GnomAD4 genome

AF:

0.000737

AC:

112

AN:

152038

Hom.:

Cov.:

AF XY:

0.000632

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000984

Gnomad4 ASJ

AF:

0.0194

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00241

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00126

AC:

ExAC

AF:

0.000795

AC:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hearing loss, autosomal recessive

Pathogenic:1

Jul 06, 2019

Laboratory of Prof. Karen Avraham, Tel Aviv University

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

Recessive, compound heterozygous with NM_001354587.1: 2589T>G; congenital, moderate-severe progressive SNHL -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.90

CADD

Benign

DANN

Benign

0.38

Eigen

Benign

0.059

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.023

GERP RS

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.73

SpliceAI score (max)

0.94

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.49

Position offset: 2

DS_AL_spliceai

0.94

Position offset: 1

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