12-123774273-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.23

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 Benign. Variant got -10 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_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH10	NM_001372106.1	c.621+9G>A		intron_variant		ENST00000673944.1
LOC105370044	XR_945481.4	n.496-9025C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH10	ENST00000673944.1	c.621+9G>A		intron_variant			NM_001372106.1	P1
DNAH10	ENST00000409039.8	c.621+9G>A		intron_variant		5
DNAH10	ENST00000614082.1	c.-109+9G>A		intron_variant		5
DNAH10	ENST00000638045.1	c.438+9G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00449 AC: 684 AN: 152212 Hom.: 1 Cov.: 33

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.: 4 AF XY: 0.00107 AC XY: 127 AN XY: 118756

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.: 6 Cov.: 23 AF XY: 0.000568 AC XY: 397 AN XY: 699490

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.: 1 Cov.: 33 AF XY: 0.00405 AC XY: 302 AN XY: 74496

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.: 2

Bravo AF: 0.00523

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 02, 2018

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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

Other links and lift over

dbSNP: rs202082455; hg19: chr12-124258820;