chr2-195782165-T-C

Variant names:

• chr2-195782165-T-C
• rs7596121
• NM_018897.3:c.10879-4180A>G

Variant summary

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

The NM_018897.3(DNAH7):​c.10879-4180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,234 control chromosomes in the GnomAD database, including 2,207 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 (2207 hom., cov: 32)
• Consequence: DNAH7 NM_018897.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 4 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018897.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	NM_018897.3	MANE Select	c.10879-4180A>G		intron	N/A	NP_061720.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	ENST00000312428.11	TSL:1 MANE Select	c.10879-4180A>G		intron	N/A	ENSP00000311273.6
	DNAH7	ENST00000409063.5	TSL:1	c.328-4180A>G		intron	N/A	ENSP00000386912.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23513 AN: 152116 Hom.: 2205 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0869

Gnomad FIN AF: 0.0804

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.155 AC: 23534 AN: 152234 Hom.: 2207 Cov.: 32 AF XY: 0.150 AC XY: 11147 AN XY: 74458

African (AFR) AF: 0.255 AC: 10566 AN: 41510

American (AMR) AF: 0.116 AC: 1775 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3472

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

South Asian (SAS) AF: 0.0870 AC: 419 AN: 4816

European-Finnish (FIN) AF: 0.0804 AC: 854 AN: 10618

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8922 AN: 68022

Other (OTH) AF: 0.161 AC: 340 AN: 2112

Alfa AF: 0.141 Hom.: 331

Bravo AF: 0.163

Asia WGS AF: 0.0580 AC: 202 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.8
DANN	Benign	0.87
PhyloP100		-0.0010
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: rs7596121; hg19: chr2-196646889; COSMIC: COSV56755322;