rs33935373

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001372106.1(DNAH10):c.6311C>T(p.Thr2104Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0359 in 1,603,722 control chromosomes in the GnomAD database, including 1,220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 61 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1159 hom. )

Consequence

DNAH10
NM_001372106.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.89

Variant links:

Genes affected

DNAH10 (HGNC:2941): (dynein axonemal heavy chain 10) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH10 is an inner arm dynein heavy chain (Maiti et al., 2000 [PubMed 11175280]).[supplied by OMIM, Mar 2008]

DNAH10 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=0.008422822).

BP6

Variant 12-123853225-C-T is Benign according to our data. Variant chr12-123853225-C-T is described in ClinVar as [Benign]. Clinvar id is 402617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-123853225-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0244 (3704/151884) while in subpopulation NFE AF= 0.0385 (2615/67984). AF 95% confidence interval is 0.0372. There are 61 homozygotes in gnomad4. There are 1828 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1 link	c.6311C>T	p.Thr2104Met	missense_variant	Exon 36 of 79	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH10	ENST00000673944.1 link	c.6311C>T	p.Thr2104Met	missense_variant	Exon 36 of 79		NM_001372106.1	ENSP00000501095.1	A0A669KB38
DNAH10	ENST00000409039.8 link	c.6140C>T	p.Thr2047Met	missense_variant	Exon 35 of 78	5		ENSP00000386770.4	A0A1C7CYW8
DNAH10	ENST00000638045.1 link	c.5957C>T	p.Thr1986Met	missense_variant	Exon 35 of 78	5		ENSP00000489675.1	Q8IVF4-1
DNAH10	ENST00000497783.3 link	n.1499C>T		non_coding_transcript_exon_variant	Exon 9 of 21	2		ENSP00000444761.2	F5H515

Frequencies

GnomAD3 genomes

AF:

0.0244

AC:

3706

AN:

151766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00686

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.00932

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0341

Gnomad FIN

AF:

0.0396

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0385

Gnomad OTH

AF:

0.0211

GnomAD3 exomes

AF:

0.0281

AC:

6706

AN:

238310

Hom.:

146

AF XY:

0.0298

AC XY:

3844

AN XY:

129206

show subpopulations

Gnomad AFR exome

AF:

0.00515

Gnomad AMR exome

AF:

0.00989

Gnomad ASJ exome

AF:

0.00751

Gnomad EAS exome

AF:

0.000287

Gnomad SAS exome

AF:

0.0350

Gnomad FIN exome

AF:

0.0374

Gnomad NFE exome

AF:

0.0395

Gnomad OTH exome

AF:

0.0280

GnomAD4 exome

AF:

0.0372

AC:

53941

AN:

1451838

Hom.:

1159

Cov.:

AF XY:

0.0370

AC XY:

26705

AN XY:

721618

show subpopulations

Gnomad4 AFR exome

AF:

0.00551

Gnomad4 AMR exome

AF:

0.0104

Gnomad4 ASJ exome

AF:

0.00790

Gnomad4 EAS exome

AF:

0.000380

Gnomad4 SAS exome

AF:

0.0357

Gnomad4 FIN exome

AF:

0.0371

Gnomad4 NFE exome

AF:

0.0417

Gnomad4 OTH exome

AF:

0.0303

GnomAD4 genome

AF:

0.0244

AC:

3704

AN:

151884

Hom.:

Cov.:

AF XY:

0.0246

AC XY:

1828

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.00684

Gnomad4 AMR

AF:

0.00931

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0341

Gnomad4 FIN

AF:

0.0396

Gnomad4 NFE

AF:

0.0385

Gnomad4 OTH

AF:

0.0209

Alfa

AF:

0.0333

Hom.:

153

Bravo

AF:

0.0208

TwinsUK

AF:

0.0405

AC:

150

ALSPAC

AF:

0.0381

AC:

147

ESP6500AA

AF:

0.00585

AC:

ESP6500EA

AF:

0.0398

AC:

326

ExAC

AF:

0.0292

AC:

3532

Asia WGS

AF:

0.0200

AC:

AN:

3478

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

0.20

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

.;T

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D

MetaRNN

Benign

0.0084

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.4

.;M

PrimateAI

Uncertain

0.79

REVEL

Uncertain

0.30

Polyphen

1.0

.;D

MPC

0.65

ClinPred

0.053

GERP RS

5.7

Varity_R

0.69

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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