12-123771606-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2 BP4_Strong BP6_Moderate

The NM_001372106.1(DNAH10):c.304C>T(p.Arg102Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000468 in 1,613,236 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R102H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00057 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (2 hom.)
• Consequence: DNAH10 NM_001372106.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.605

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]

LOC105370044 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PP2: Missense variant where missense usually causes diseases, DNAH10
• BP4: Computational evidence support a benign effect (MetaRNN=0.0057855844).
• BP6: Variant 12-123771606-C-T is Benign according to our data. Variant chr12-123771606-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3049615.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH10	NM_001372106.1	c.304C>T	p.Arg102Cys	missense_variant	3/79	ENST00000673944.1
LOC105370044	XR_945481.4	n.496-6358G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH10	ENST00000673944.1	c.304C>T	p.Arg102Cys	missense_variant	3/79		NM_001372106.1	P1
DNAH10	ENST00000409039.8	c.304C>T	p.Arg102Cys	missense_variant	3/78	5
DNAH10	ENST00000638045.1	c.121C>T	p.Arg41Cys	missense_variant	3/78	5
DNAH10	ENST00000614082.1	c.-426C>T		5_prime_UTR_variant	3/20	5

Frequencies

GnomAD3 genomes AF: 0.000572 AC: 87 AN: 152146 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000677 AC: 168 AN: 248106 Hom.: 0 AF XY: 0.000832 AC XY: 112 AN XY: 134562

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000872

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00145

Gnomad FIN exome AF: 0.00288

Gnomad NFE exome AF: 0.000480

Gnomad OTH exome AF: 0.000830

GnomAD4 exome AF: 0.000457 AC: 668 AN: 1460972 Hom.: 2 Cov.: 30 AF XY: 0.000553 AC XY: 402 AN XY: 726682

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00172

Gnomad4 FIN exome AF: 0.00337

Gnomad4 NFE exome AF: 0.000270

Gnomad4 OTH exome AF: 0.000547

GnomAD4 genome AF: 0.000571 AC: 87 AN: 152264 Hom.: 1 Cov.: 32 AF XY: 0.000712 AC XY: 53 AN XY: 74454

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.000706

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000445 Hom.: 1

Bravo AF: 0.000223

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000365 AC: 3

ExAC AF: 0.000737 AC: 89

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000297

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

DNAH10-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as likely 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
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	14
Dann	Benign	0.51
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.0058	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
REVEL	Benign	0.041
Polyphen		0.13	.;B
MVP		0.061
MPC		0.20
ClinPred		0.021	T
GERP RS		-0.59
Varity_R		0.069
gMVP		0.29

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

Other links and lift over

dbSNP: rs200881150; hg19: chr12-124256153;