rs72658841

Variant names:

• chr7-21901270-C-T
• rs72658841
• NM_001277115.2:c.*16C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001277115.2(DNAH11):​c.*16C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00309 in 1,587,120 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (54 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (66 hom.)
• Consequence: DNAH11 NM_001277115.2 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.285
• 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=-0.87).
• BP6: Variant 7-21901270-C-T is Benign according to our data. Variant chr7-21901270-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

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.*16C>T		3_prime_UTR	Exon 82 of 82	NP_001264044.1	Q96DT5
	CDCA7L	NM_018719.5	MANE Select	c.*1052G>A		3_prime_UTR	Exon 10 of 10	NP_061189.2
	CDCA7L	NM_001127370.3		c.*1052G>A		3_prime_UTR	Exon 11 of 11	NP_001120842.1	Q96GN5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.*16C>T		3_prime_UTR	Exon 82 of 82	ENSP00000475939.1	Q96DT5
	CDCA7L	ENST00000406877.8	TSL:1 MANE Select	c.*1052G>A		3_prime_UTR	Exon 10 of 10	ENSP00000383986.3	Q96GN5-1
	CDCA7L	ENST00000934293.1		c.*1052G>A		3_prime_UTR	Exon 10 of 10	ENSP00000604352.1

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2364 AN: 146262 Hom.: 54 Cov.: 33

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00699

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000489

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00645

Gnomad NFE AF: 0.000276

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00478 AC: 1079 AN: 225632 AF XY: 0.00360

Gnomad AFR exome AF: 0.0593

Gnomad AMR exome AF: 0.00431

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000294

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00176 AC: 2536 AN: 1440772 Hom.: 66 Cov.: 33 AF XY: 0.00154 AC XY: 1098 AN XY: 714302

African (AFR) AF: 0.0576 AC: 1897 AN: 32954

American (AMR) AF: 0.00426 AC: 184 AN: 43218

Ashkenazi Jewish (ASJ) AF: 0.0000807 AC: 2 AN: 24778

East Asian (EAS) AF: 0.00 AC: 0 AN: 39294

South Asian (SAS) AF: 0.0000613 AC: 5 AN: 81604

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52712

Middle Eastern (MID) AF: 0.00389 AC: 22 AN: 5650

European-Non Finnish (NFE) AF: 0.000197 AC: 217 AN: 1101152

Other (OTH) AF: 0.00350 AC: 208 AN: 59410

GnomAD4 genome AF: 0.0161 AC: 2362 AN: 146348 Hom.: 54 Cov.: 33 AF XY: 0.0159 AC XY: 1138 AN XY: 71498

African (AFR) AF: 0.0548 AC: 2208 AN: 40326

American (AMR) AF: 0.00698 AC: 105 AN: 15034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3314

East Asian (EAS) AF: 0.00 AC: 0 AN: 4918

South Asian (SAS) AF: 0.000245 AC: 1 AN: 4082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10306

Middle Eastern (MID) AF: 0.00690 AC: 2 AN: 290

European-Non Finnish (NFE) AF: 0.000276 AC: 18 AN: 65290

Other (OTH) AF: 0.0138 AC: 28 AN: 2028

Alfa AF: 0.00648 Hom.: 6

Bravo AF: 0.0181

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.62
PhyloP100		-0.28
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: rs72658841; hg19: chr7-21940888;