rs1990236

Positions:

• chr17-11962145-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001372.4(DNAH9):​c.13122G>A​(p.Met4374Ile) variant causes a missense change. The variant allele was found at a frequency of 0.182 in 1,613,930 control chromosomes in the GnomAD database, including 27,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (2395 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25125 hom.)
• Consequence: DNAH9 NM_001372.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 6.83

Genes affected

DNAH9 (HGNC:2953): (dynein axonemal heavy chain 9) This gene encodes the heavy chain subunit of axonemal dynein, a large multi-subunit molecular motor. Axonemal dynein attaches to microtubules and hydrolyzes ATP to mediate the movement of cilia and flagella. The gene expresses at least two transcript variants; additional variants have been described, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001670748).
• BP6: Variant 17-11962145-G-A is Benign according to our data. Variant chr17-11962145-G-A is described in ClinVar as [Benign]. Clinvar id is 402788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH9	NM_001372.4	c.13122G>A	p.Met4374Ile	missense_variant	68/69	ENST00000262442.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH9	ENST00000262442.9	c.13122G>A	p.Met4374Ile	missense_variant	68/69	1	NM_001372.4	P1
	ENST00000580270.1	n.348-8141C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26329 AN: 151962 Hom.: 2390 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.177

GnomAD3 exomes AF: 0.190 AC: 47605 AN: 250890 Hom.: 4804 AF XY: 0.185 AC XY: 25101 AN XY: 135574

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.192

Gnomad SAS exome AF: 0.142

Gnomad FIN exome AF: 0.204

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.193

GnomAD4 exome AF: 0.183 AC: 267642 AN: 1461850 Hom.: 25125 Cov.: 33 AF XY: 0.181 AC XY: 131611 AN XY: 727230

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.270

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.181

GnomAD4 genome AF: 0.173 AC: 26356 AN: 152080 Hom.: 2395 Cov.: 32 AF XY: 0.173 AC XY: 12895 AN XY: 74338

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.178

Alfa AF: 0.183 Hom.: 6450

Bravo AF: 0.176

TwinsUK AF: 0.196 AC: 727

ALSPAC AF: 0.187 AC: 719

ESP6500AA AF: 0.126 AC: 555

ESP6500EA AF: 0.179 AC: 1538

ExAC AF: 0.184 AC: 22337

Asia WGS AF: 0.156 AC: 542 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 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
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.064	T;.;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.75	T;T;T
MetaRNN	Benign	0.0017	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	L;.;.
MutationTaster	Benign	0.0000022	P;P;P
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.4	D;D;.
REVEL	Benign	0.15
Sift	Uncertain	0.021	D;D;.
Sift4G	Uncertain	0.032	.;.;D
Polyphen		0.35	B;.;.
Vest4		0.21
MutPred		0.61		Loss of disorder (P = 0.0837);.;.;
MPC		0.15
ClinPred		0.018	T
GERP RS		4.0
Varity_R		0.62
gMVP		0.41

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: rs1990236; hg19: chr17-11865462; COSMIC: COSV52349972;