rs6434804

Variant names:

• chr2-195899669-T-G
• rs6434804
• NM_018897.3:c.4548+613A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018897.3(DNAH7):​c.4548+613A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,166 control chromosomes in the GnomAD database, including 2,947 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 0.17 (2947 hom., cov: 32)
• Consequence: DNAH7 NM_018897.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.884
• Publications: 3 publications found

Genes affected

DNAH7 (HGNC:18661): (dynein axonemal heavy chain 7) DNAH7 is a component of the inner dynein arm of ciliary axonemes (Zhang et al., 2002 [PubMed 11877439]).[supplied by OMIM, Mar 2008]

DNAH7 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 50

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: LIMITED Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH7	NM_018897.3	c.4548+613A>C		intron_variant	Intron 28 of 64	ENST00000312428.11	NP_061720.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000312428.11	c.4548+613A>C		intron_variant	Intron 28 of 64	1	NM_018897.3	ENSP00000311273.6
DNAH7	ENST00000475293.1	n.5481+613A>C		intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26153 AN: 152048 Hom.: 2942 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0882

Gnomad FIN AF: 0.0801

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.172 AC: 26196 AN: 152166 Hom.: 2947 Cov.: 32 AF XY: 0.167 AC XY: 12443 AN XY: 74396

African (AFR) AF: 0.315 AC: 13077 AN: 41482

American (AMR) AF: 0.121 AC: 1849 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 528 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5192

South Asian (SAS) AF: 0.0884 AC: 427 AN: 4828

European-Finnish (FIN) AF: 0.0801 AC: 849 AN: 10598

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.131 AC: 8937 AN: 67992

Other (OTH) AF: 0.174 AC: 367 AN: 2112

Alfa AF: 0.155 Hom.: 310

Bravo AF: 0.183

Asia WGS AF: 0.0620 AC: 215 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6434804; hg19: chr2-196764393;