rs11057354

chr12-123783091-A-Gchr12-123783091-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001372106.1(DNAH10):c.842-16A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 1,611,744 control chromosomes in the GnomAD database, including 652,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.92 (64640 hom., cov: 32)
  • Exomes 𝑓: 0.90 (588084 hom.)
• Consequence: DNAH10 NM_001372106.1 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.77

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-123783091-A-G is Benign according to our data. Variant chr12-123783091-A-G is described in ClinVar as [Benign]. Clinvar id is 402612.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-123783091-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH10	NM_001372106.1	c.842-16A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000673944.1
LOC105370044	XR_945481.4	n.495+5402T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH10	ENST00000673944.1	c.842-16A>G		splice_polypyrimidine_tract_variant, intron_variant			NM_001372106.1	P1

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139914 AN: 152102 Hom.: 64585 Cov.: 32

Gnomad AFR AF: 0.980

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.966

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.939

GnomAD3 exomes AF: 0.907 AC: 227423 AN: 250710 Hom.: 103547 AF XY: 0.910 AC XY: 123292 AN XY: 135466

Gnomad AFR exome AF: 0.982

Gnomad AMR exome AF: 0.863

Gnomad ASJ exome AF: 0.943

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.957

Gnomad FIN exome AF: 0.811

Gnomad NFE exome AF: 0.896

Gnomad OTH exome AF: 0.911

GnomAD4 exome AF: 0.897 AC: 1309042 AN: 1459524 Hom.: 588084 Cov.: 34 AF XY: 0.899 AC XY: 653072 AN XY: 726072

Gnomad4 AFR exome AF: 0.983

Gnomad4 AMR exome AF: 0.870

Gnomad4 ASJ exome AF: 0.940

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.957

Gnomad4 FIN exome AF: 0.819

Gnomad4 NFE exome AF: 0.889

Gnomad4 OTH exome AF: 0.912

GnomAD4 genome AF: 0.920 AC: 140027 AN: 152220 Hom.: 64640 Cov.: 32 AF XY: 0.918 AC XY: 68315 AN XY: 74418

Gnomad4 AFR AF: 0.980

Gnomad4 AMR AF: 0.906

Gnomad4 ASJ AF: 0.947

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.964

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.892

Gnomad4 OTH AF: 0.940

Alfa AF: 0.903 Hom.: 34394

Bravo AF: 0.928

Asia WGS AF: 0.980 AC: 3408 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.0060
Dann	Benign	0.28

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: rs11057354; hg19: chr12-124267638;