Variant rs4681982 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001366028.2(DNAH12):c.5253+289C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,166,838 control chromosomes in the GnomAD database, including 130,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 25133 hom., cov: 32)

Exomes 𝑓: 0.45 ( 104935 hom. )

Consequence

DNAH12
NM_001366028.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.401

Variant links:

Genes affected

DNAH12 (HGNC:2943): (dynein axonemal heavy chain 12) Predicted to enable several functions, including ATP binding activity; dynein intermediate chain binding activity; and dynein light intermediate chain binding activity. Predicted to be involved in microtubule-based movement. Predicted to be located in cilium; cytoplasm; and microtubule. Predicted to be part of dynein complex. [provided by Alliance of Genome Resources, Apr 2022]

DNAH12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.9716767E-6).

BP6

Variant 3-57428344-G-A is Benign according to our data. Variant chr3-57428344-G-A is described in ClinVar as [Benign]. Clinvar id is 402633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH12	NM_001366028.2 link	c.5253+289C>T		intron_variant		ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6 link	c.5253+289C>T		intron_variant		5	NM_001366028.2	ENSP00000418137.2		E9PG32
DNAH12	ENST00000351747.6 link	c.5288C>T	p.Thr1763Ile	missense_variant	35/59	5		ENSP00000295937.3		Q6ZR08-1

Frequencies

GnomAD3 genomes

AF:

0.559

AC:

84968

AN:

151960

Hom.:

25114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.764

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.557

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.578

Gnomad FIN

AF:

0.510

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.529

GnomAD3 exomes

AF:

0.500

AC:

67160

AN:

134268

Hom.:

17290

AF XY:

0.500

AC XY:

35604

AN XY:

71182

show subpopulations

Gnomad AFR exome

AF:

0.775

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.448

Gnomad EAS exome

AF:

0.414

Gnomad SAS exome

AF:

0.562

Gnomad FIN exome

AF:

0.505

Gnomad NFE exome

AF:

0.460

Gnomad OTH exome

AF:

0.486

GnomAD4 exome

AF:

0.449

AC:

455352

AN:

1014760

Hom.:

104935

Cov.:

AF XY:

0.453

AC XY:

229186

AN XY:

505868

show subpopulations

Gnomad4 AFR exome

AF:

0.759

Gnomad4 AMR exome

AF:

0.514

Gnomad4 ASJ exome

AF:

0.431

Gnomad4 EAS exome

AF:

0.418

Gnomad4 SAS exome

AF:

0.550

Gnomad4 FIN exome

AF:

0.505

Gnomad4 NFE exome

AF:

0.428

Gnomad4 OTH exome

AF:

0.468

GnomAD4 genome

AF:

0.559

AC:

85044

AN:

152078

Hom.:

25133

Cov.:

AF XY:

0.562

AC XY:

41756

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.764

Gnomad4 AMR

AF:

0.556

Gnomad4 ASJ

AF:

0.428

Gnomad4 EAS

AF:

0.420

Gnomad4 SAS

AF:

0.579

Gnomad4 FIN

AF:

0.510

Gnomad4 NFE

AF:

0.461

Gnomad4 OTH

AF:

0.530

Alfa

AF:

0.470

Hom.:

12007

Bravo

AF:

0.566

TwinsUK

AF:

0.449

AC:

1665

ALSPAC

AF:

0.458

AC:

1765

ExAC

AF:

0.511

AC:

10565

Asia WGS

AF:

0.552

AC:

1918

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.88

DANN

Benign

0.62

DEOGEN2

Benign

0.0067

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.000070

LIST_S2

Benign

0.21

MetaRNN

Benign

0.0000020

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.92

REVEL

Benign

0.040

Sift

Benign

0.062

Polyphen

0.0

Vest4

0.0060

ClinPred

0.0061

GERP RS

-0.55

Varity_R

0.039

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