17-7733155-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_020877.5(DNAH2):c.468A>T(p.Ala156=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000821 in 1,614,188 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00079 (12 hom.)
• Consequence: DNAH2 NM_020877.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.96

Genes affected

DNAH2 (HGNC:2948): (dynein axonemal heavy chain 2) 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. DNAH2 is an axonemal inner arm dynein heavy chain (Chapelin et al., 1997 [PubMed 9256245]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-7733155-A-T is Benign according to our data. Variant chr17-7733155-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2647369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.96 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00114 (174/152308) while in subpopulation AFR AF= 0.000673 (28/41574). AF 95% confidence interval is 0.000478. There are 4 homozygotes in gnomad4. There are 85 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH2	NM_020877.5	c.468A>T	p.Ala156=	synonymous_variant	5/86	ENST00000572933.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH2	ENST00000572933.6	c.468A>T	p.Ala156=	synonymous_variant	5/86	2	NM_020877.5	P1
DNAH2	ENST00000570791.5	c.468A>T	p.Ala156=	synonymous_variant	5/14	1
DNAH2	ENST00000389173.6	c.468A>T	p.Ala156=	synonymous_variant	4/85	2		P1

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 171 AN: 152190 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00137 AC: 344 AN: 251430 Hom.: 3 AF XY: 0.00124 AC XY: 168 AN XY: 135894

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.0256

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000787 AC: 1151 AN: 1461880 Hom.: 12 Cov.: 31 AF XY: 0.000811 AC XY: 590 AN XY: 727240

Gnomad4 AFR exome AF: 0.00242

Gnomad4 AMR exome AF: 0.000648

Gnomad4 ASJ exome AF: 0.0246

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000200

Gnomad4 OTH exome AF: 0.00243

GnomAD4 genome AF: 0.00114 AC: 174 AN: 152308 Hom.: 4 Cov.: 31 AF XY: 0.00114 AC XY: 85 AN XY: 74488

Gnomad4 AFR AF: 0.000673

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.0302

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00246 Hom.: 2

Bravo AF: 0.00117

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000771

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

DNAH2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 21, 2019

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). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

DNAH2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.10
Dann	Benign	0.53

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: rs144172284; hg19: chr17-7636473;