dbSNP rs202082455: DNAH10:c.621+9G>A (chr12-123774273-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001372106.1(DNAH10):c.621+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,557,024 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00063 ( 6 hom. )

Consequence

DNAH10
NM_001372106.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.23

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:

LOC105370044 (HGNC:):

LOC105370044 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-123774273-G-A is Benign according to our data. Variant chr12-123774273-G-A is described in ClinVar as [Benign]. Clinvar id is 708810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH10	NM_001372106.1 link	c.621+9G>A		intron_variant	Intron 5 of 78	ENST00000673944.1	NP_001359035.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH10	ENST00000673944.1 link	c.621+9G>A	intron_variant	Intron 5 of 78		NM_001372106.1	ENSP00000501095.1	A0A669KB38
DNAH10	ENST00000409039.8 link	c.621+9G>A	intron_variant	Intron 5 of 77	5		ENSP00000386770.4	A0A1C7CYW8
DNAH10	ENST00000638045.1 link	c.438+9G>A	intron_variant	Intron 5 of 77	5		ENSP00000489675.1	Q8IVF4-1
DNAH10	ENST00000614082.1 link	c.-109+9G>A	intron_variant	Intron 5 of 19	5		ENSP00000479072.1	A0A087WV07

Frequencies

GnomAD3 genomes

AF:

0.00449

AC:

684

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00141

AC:

308

AN:

217868

Hom.:

AF XY:

0.00107

AC XY:

127

AN XY:

118756

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00580

Gnomad EAS exome

AF:

0.000557

Gnomad SAS exome

AF:

0.0000414

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000144

Gnomad OTH exome

AF:

0.000982

GnomAD4 exome

AF:

0.000626

AC:

880

AN:

1404694

Hom.:

Cov.:

AF XY:

0.000568

AC XY:

397

AN XY:

699490

show subpopulations

Gnomad4 AFR exome

AF:

0.0144

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.00508

Gnomad4 EAS exome

AF:

0.000281

Gnomad4 SAS exome

AF:

0.0000376

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000133

Gnomad4 OTH exome

AF:

0.00140

GnomAD4 genome

AF:

0.00449

AC:

684

AN:

152330

Hom.:

Cov.:

AF XY:

0.00405

AC XY:

302

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0146

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00347

Hom.:

Bravo

AF:

0.00523

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 02, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

DNAH10-related disorder

Benign:1

Aug 17, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.1

DANN

Benign

0.51

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