rs1544725

Positions:

• chr17-7718559-C-A

Variant summary

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

The NM_020877.5(DNAH2):​c.-255C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,240 control chromosomes in the GnomAD database, including 2,364 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 0.15 (2364 hom., cov: 32)
  • Exomes 𝑓: 0.041 (0 hom.)
• Consequence: DNAH2 NM_020877.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH2	NM_020877.5	c.-255C>A		5_prime_UTR_variant	1/86	ENST00000572933.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH2	ENST00000572933.6	c.-255C>A		5_prime_UTR_variant	1/86	2	NM_020877.5	P1
DNAH2	ENST00000570791.5	c.-15+728C>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23196 AN: 151998 Hom.: 2361 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0792

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0912

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.0410 AC: 5 AN: 122 Hom.: 0 Cov.: 0 AF XY: 0.0395 AC XY: 3 AN XY: 76

Gnomad4 FIN exome AF: 0.0364

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.153 AC: 23216 AN: 152118 Hom.: 2364 Cov.: 32 AF XY: 0.151 AC XY: 11198 AN XY: 74372

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.0792

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.0520

Gnomad4 NFE AF: 0.0912

Gnomad4 OTH AF: 0.129

Alfa AF: 0.104 Hom.: 1042

Bravo AF: 0.164

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.1
DANN	Benign	0.89

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: rs1544725; hg19: chr17-7621877;