17-7730374-C-T

Position:

• chr17-7730374-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020877.5(DNAH2):​c.400-2713C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 151,980 control chromosomes in the GnomAD database, including 985 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (985 hom., cov: 32)
• Consequence: DNAH2 NM_020877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH2	NM_020877.5	c.400-2713C>T		intron_variant		ENST00000572933.6	NP_065928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH2	ENST00000572933.6	c.400-2713C>T		intron_variant		2	NM_020877.5	ENSP00000458355	P1
DNAH2	ENST00000570791.5	c.400-2713C>T		intron_variant		1		ENSP00000460245
DNAH2	ENST00000389173.6	c.400-2713C>T		intron_variant		2		ENSP00000373825	P1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16269 AN: 151862 Hom.: 982 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.0705

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0994

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.107 AC: 16289 AN: 151980 Hom.: 985 Cov.: 32 AF XY: 0.103 AC XY: 7614 AN XY: 74272

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0703

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0820

Gnomad4 FIN AF: 0.0925

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.0984

Alfa AF: 0.110 Hom.: 1925

Bravo AF: 0.106

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.2
DANN	Benign	0.82

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: rs16956936; hg19: chr17-7633692;