rs186895

Variant names:

• chr2-195901785-C-T
• rs186895
• ENST00000475293.1:n.3978G>A

Variant summary

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

The ENST00000475293.1(DNAH7):​n.3978G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,752 control chromosomes in the GnomAD database, including 10,040 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 0.32 (10040 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DNAH7 ENST00000475293.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH7	NM_018897.3	c.4336-1291G>A		intron_variant	Intron 27 of 64	ENST00000312428.11	NP_061720.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH7	ENST00000475293.1	n.3978G>A		non_coding_transcript_exon_variant	Exon 1 of 3	1
DNAH7	ENST00000312428.11	c.4336-1291G>A		intron_variant	Intron 27 of 64	1	NM_018897.3	ENSP00000311273.6

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47856 AN: 151634 Hom.: 10006 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.240

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.307

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.316 AC: 47947 AN: 151752 Hom.: 10040 Cov.: 32 AF XY: 0.310 AC XY: 22988 AN XY: 74172

African (AFR) AF: 0.599 AC: 24786 AN: 41382

American (AMR) AF: 0.232 AC: 3533 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 882 AN: 3466

East Asian (EAS) AF: 0.0729 AC: 377 AN: 5170

South Asian (SAS) AF: 0.164 AC: 788 AN: 4800

European-Finnish (FIN) AF: 0.191 AC: 2005 AN: 10494

Middle Eastern (MID) AF: 0.241 AC: 70 AN: 290

European-Non Finnish (NFE) AF: 0.216 AC: 14649 AN: 67896

Other (OTH) AF: 0.309 AC: 653 AN: 2112

Alfa AF: 0.240 Hom.: 3421

Bravo AF: 0.333

Asia WGS AF: 0.168 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.71
PhyloP100		-1.4
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: rs186895; hg19: chr2-196766509;