rs72658832

Variant names:

• chr7-21899961-T-A
• rs72658832
• NM_001277115.2:c.13163-19T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001277115.2(DNAH11):​c.13163-19T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,612,826 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (28 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.534
• Publications: 0 publications found

Genes affected

DNAH11 (HGNC:2942): (dynein axonemal heavy chain 11) This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility. [provided by RefSeq, Mar 2013]

CDCA7L (HGNC:30777): (cell division cycle associated 7 like) Acts upstream of or within positive regulation of cell population proliferation. Located in cytosol; fibrillar center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-21899961-T-A is Benign according to our data. Variant chr7-21899961-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00321 (488/152240) while in subpopulation SAS AF = 0.0085 (41/4826). AF 95% confidence interval is 0.00644. There are 2 homozygotes in GnomAd4. There are 238 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277115.2. 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
	DNAH11	NM_001277115.2	MANE Select	c.13163-19T>A		intron	N/A	NP_001264044.1	Q96DT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.13163-19T>A		intron	N/A	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000479878.1	TSL:3	n.534-19T>A		intron	N/A
	CDCA7L	ENST00000904741.1		c.*2361A>T		downstream_gene	N/A	ENSP00000574800.1

Frequencies

GnomAD3 genomes AF: 0.00321 AC: 489 AN: 152122 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00468

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00422 AC: 1045 AN: 247470 AF XY: 0.00475

Gnomad AFR exome AF: 0.000584

Gnomad AMR exome AF: 0.00363

Gnomad ASJ exome AF: 0.00793

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00121

Gnomad NFE exome AF: 0.00470

Gnomad OTH exome AF: 0.00383

GnomAD4 exome AF: 0.00416 AC: 6082 AN: 1460586 Hom.: 28 Cov.: 31 AF XY: 0.00445 AC XY: 3232 AN XY: 726542

African (AFR) AF: 0.000629 AC: 21 AN: 33386

American (AMR) AF: 0.00362 AC: 161 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.00897 AC: 234 AN: 26092

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39682

South Asian (SAS) AF: 0.00794 AC: 684 AN: 86106

European-Finnish (FIN) AF: 0.00137 AC: 73 AN: 53370

Middle Eastern (MID) AF: 0.00851 AC: 49 AN: 5758

European-Non Finnish (NFE) AF: 0.00419 AC: 4655 AN: 1111378

Other (OTH) AF: 0.00338 AC: 204 AN: 60312

GnomAD4 genome AF: 0.00321 AC: 488 AN: 152240 Hom.: 2 Cov.: 33 AF XY: 0.00320 AC XY: 238 AN XY: 74434

African (AFR) AF: 0.000458 AC: 19 AN: 41530

American (AMR) AF: 0.00386 AC: 59 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00850 AC: 41 AN: 4826

European-Finnish (FIN) AF: 0.000942 AC: 10 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00468 AC: 318 AN: 68006

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.00418 Hom.: 1

Bravo AF: 0.00346

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.20
DANN	Benign	0.51
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs72658832; hg19: chr7-21939579;