rs72658841

chr7-21901270-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.*16C>T		3_prime_UTR_variant	82/82	ENST00000409508.8
CDCA7L	NM_018719.5	c.*1052G>A		3_prime_UTR_variant	10/10	ENST00000406877.8
CDCA7L	NM_001127370.3	c.*1052G>A		3_prime_UTR_variant	11/11
CDCA7L	NM_001127371.3	c.*1052G>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDCA7L	ENST00000406877.8	c.*1052G>A		3_prime_UTR_variant	10/10	1	NM_018719.5	P1
DNAH11	ENST00000409508.8	c.*16C>T		3_prime_UTR_variant	82/82	5	NM_001277115.2	P1
CDCA7L	ENST00000356195.9	c.*1052G>A		3_prime_UTR_variant	11/11	2
CDCA7L	ENST00000488845.1	n.1574G>A		non_coding_transcript_exon_variant	4/4	2

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

GnomAD3 exomes AF: 0.00478 AC: 1079 AN: 225632 Hom.: 25 AF XY: 0.00360 AC XY: 438 AN XY: 121600

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 SAS exome AF: 0.0000810

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

Gnomad4 AFR exome AF: 0.0576

Gnomad4 AMR exome AF: 0.00426

Gnomad4 ASJ exome AF: 0.0000807

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000613

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.000197

Gnomad4 OTH exome AF: 0.00350

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

Gnomad4 AFR AF: 0.0548

Gnomad4 AMR AF: 0.00698

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000245

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000276

Gnomad4 OTH AF: 0.0138

Alfa AF: 0.00570 Hom.: 4

Bravo AF: 0.0181

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 06, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.7
Dann	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs72658841; hg19: chr7-21940888;