rs115124743

Variant names:

• chr2-195960532-G-C
• rs115124743
• NM_018897.3:c.2619C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018897.3(DNAH7):​c.2619C>G​(p.Val873Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0341 in 1,614,102 control chromosomes in the GnomAD database, including 1,005 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (85 hom., cov: 32)
  • Exomes 𝑓: 0.034 (920 hom.)
• Consequence: DNAH7 NM_018897.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0290
• 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: ClinGen, 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-195960532-G-C is Benign according to our data. Variant chr2-195960532-G-C is described in ClinVar as Benign. ClinVar VariationId is 402754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.029 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0609 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	NM_018897.3	MANE Select	c.2619C>G	p.Val873Val	synonymous	Exon 18 of 65	NP_061720.2	Q8WXX0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH7	ENST00000312428.11	TSL:1 MANE Select	c.2619C>G	p.Val873Val	synonymous	Exon 18 of 65	ENSP00000311273.6	Q8WXX0-1

Frequencies

GnomAD3 genomes AF: 0.0302 AC: 4588 AN: 152116 Hom.: 85 Cov.: 32

Gnomad AFR AF: 0.00934

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0380

Gnomad ASJ AF: 0.0328

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.0497

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0408

Gnomad OTH AF: 0.0321

GnomAD2 exomes AF: 0.0291 AC: 7260 AN: 249194 AF XY: 0.0305

Gnomad AFR exome AF: 0.00756

Gnomad AMR exome AF: 0.0248

Gnomad ASJ exome AF: 0.0292

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.0399

Gnomad NFE exome AF: 0.0395

Gnomad OTH exome AF: 0.0385

GnomAD4 exome AF: 0.0345 AC: 50383 AN: 1461868 Hom.: 920 Cov.: 31 AF XY: 0.0344 AC XY: 25047 AN XY: 727236

African (AFR) AF: 0.00762 AC: 255 AN: 33480

American (AMR) AF: 0.0268 AC: 1200 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 723 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39698

South Asian (SAS) AF: 0.0148 AC: 1278 AN: 86256

European-Finnish (FIN) AF: 0.0373 AC: 1991 AN: 53420

Middle Eastern (MID) AF: 0.0664 AC: 383 AN: 5768

European-Non Finnish (NFE) AF: 0.0382 AC: 42470 AN: 1111992

Other (OTH) AF: 0.0344 AC: 2079 AN: 60394

GnomAD4 genome AF: 0.0301 AC: 4587 AN: 152234 Hom.: 85 Cov.: 32 AF XY: 0.0305 AC XY: 2271 AN XY: 74444

African (AFR) AF: 0.00929 AC: 386 AN: 41538

American (AMR) AF: 0.0379 AC: 580 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0328 AC: 114 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.0139 AC: 67 AN: 4826

European-Finnish (FIN) AF: 0.0497 AC: 527 AN: 10600

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0408 AC: 2774 AN: 68012

Other (OTH) AF: 0.0318 AC: 67 AN: 2108

Alfa AF: 0.0361 Hom.: 34

Bravo AF: 0.0280

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.0463

EpiControl AF: 0.0460

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	DNAH7-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.54
PhyloP100		0.029
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: rs115124743; hg19: chr2-196825256;