7-21900988-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2 BP4_Strong BP6_Very_Strong

The NM_018719.5(CDCA7L):c.*1334G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000492 in 1,558,370 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (1 hom.)
• Consequence: CDCA7L NM_018719.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.97

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-21900988-C-T is Benign according to our data. Variant chr7-21900988-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1574572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDCA7L	NM_018719.5	c.*1334G>A		3_prime_UTR_variant	10/10	ENST00000406877.8
DNAH11	NM_001277115.2	c.13304-19C>T		intron_variant		ENST00000409508.8
CDCA7L	NM_001127370.3	c.*1334G>A		3_prime_UTR_variant	11/11
CDCA7L	NM_001127371.3	c.*1334G>A		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDCA7L	ENST00000406877.8	c.*1334G>A		3_prime_UTR_variant	10/10	1	NM_018719.5	P1
DNAH11	ENST00000409508.8	c.13304-19C>T		intron_variant		5	NM_001277115.2	P1

Frequencies

GnomAD3 genomes AF: 0.000646 AC: 98 AN: 151760 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000414

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000576 AC: 123 AN: 213370 Hom.: 0 AF XY: 0.000537 AC XY: 62 AN XY: 115500

Gnomad AFR exome AF: 0.000479

Gnomad AMR exome AF: 0.000825

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000481

Gnomad SAS exome AF: 0.000615

Gnomad FIN exome AF: 0.00137

Gnomad NFE exome AF: 0.000415

Gnomad OTH exome AF: 0.000608

GnomAD4 exome AF: 0.000476 AC: 669 AN: 1406492 Hom.: 1 Cov.: 33 AF XY: 0.000485 AC XY: 337 AN XY: 694384

Gnomad4 AFR exome AF: 0.000637

Gnomad4 AMR exome AF: 0.000743

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000591

Gnomad4 SAS exome AF: 0.000824

Gnomad4 FIN exome AF: 0.000869

Gnomad4 NFE exome AF: 0.000412

Gnomad4 OTH exome AF: 0.000656

GnomAD4 genome AF: 0.000645 AC: 98 AN: 151878 Hom.: 0 Cov.: 33 AF XY: 0.000673 AC XY: 50 AN XY: 74268

Gnomad4 AFR AF: 0.000413

Gnomad4 AMR AF: 0.00164

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000754

Gnomad4 NFE AF: 0.000617

Gnomad4 OTH AF: 0.000948

Bravo AF: 0.000688

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 7 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 31, 2021

- -

Primary ciliary dyskinesia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.22
Dann	Benign	0.77

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: rs141951506; hg19: chr7-21940606;