rs6445902

Variant names:

Variant summary

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

The NM_001366028.2(DNAH12):c.672T>G(p.Asp224Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,605,692 control chromosomes in the GnomAD database, including 33,301 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6410 hom., cov: 32)

Exomes 𝑓: 0.18 ( 26891 hom. )

Consequence

DNAH12
NM_001366028.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.396

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=3.632307E-4).

BP6

Variant 3-57508411-A-C is Benign according to our data. Variant chr3-57508411-A-C is described in ClinVar as [Benign]. Clinvar id is 402643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH12	NM_001366028.2 link	c.672T>G	p.Asp224Glu	missense_variant	Exon 7 of 74	ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6 link	c.672T>G	p.Asp224Glu	missense_variant	Exon 7 of 74	5	NM_001366028.2	ENSP00000418137.2		E9PG32

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38740

AN:

151934

Hom.:

6393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.0677

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.222

GnomAD3 exomes

AF:

0.179

AC:

43599

AN:

243238

Hom.:

4871

AF XY:

0.176

AC XY:

23140

AN XY:

131530

show subpopulations

Gnomad AFR exome

AF:

0.473

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.199

Gnomad EAS exome

AF:

0.0573

Gnomad SAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.155

Gnomad NFE exome

AF:

0.178

Gnomad OTH exome

AF:

0.173

GnomAD4 exome

AF:

0.184

AC:

267524

AN:

1453640

Hom.:

26891

Cov.:

AF XY:

0.183

AC XY:

132306

AN XY:

722886

show subpopulations

Gnomad4 AFR exome

AF:

0.480

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.202

Gnomad4 EAS exome

AF:

0.0761

Gnomad4 SAS exome

AF:

0.186

Gnomad4 FIN exome

AF:

0.154

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.188

GnomAD4 genome

AF:

0.255

AC:

38792

AN:

152052

Hom.:

6410

Cov.:

AF XY:

0.250

AC XY:

18554

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.471

Gnomad4 AMR

AF:

0.157

Gnomad4 ASJ

AF:

0.203

Gnomad4 EAS

AF:

0.0676

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.146

Gnomad4 NFE

AF:

0.187

Gnomad4 OTH

AF:

0.220

Alfa

AF:

0.191

Hom.:

7929

Bravo

AF:

0.266

TwinsUK

AF:

0.193

AC:

717

ALSPAC

AF:

0.182

AC:

700

ESP6500AA

AF:

0.470

AC:

2073

ESP6500EA

AF:

0.190

AC:

1636

ExAC

AF:

0.186

AC:

22618

EpiCase

AF:

0.176

EpiControl

AF:

0.176

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.4

DANN

Benign

0.91

DEOGEN2

Benign

0.0049

T;T;.;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.57

T;T;T;T

MetaRNN

Benign

0.00036

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.1

.;L;.;L

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.75

N;N;N;N

REVEL

Benign

0.022

Sift

Benign

0.39

T;T;T;T

Sift4G

Benign

0.21

.;.;T;T

Polyphen

0.0090, 0.45

.;B;.;B

Vest4

0.026

MutPred

0.23

Gain of glycosylation at T221 (P = 0.0582);Gain of glycosylation at T221 (P = 0.0582);Gain of glycosylation at T221 (P = 0.0582);Gain of glycosylation at T221 (P = 0.0582);

MPC

0.077

ClinPred

0.0030

GERP RS

-0.56

Varity_R

0.034

gMVP

0.10

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