rs150682314

Positions:

• chr7-21901008-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The ENST00000406877.8(CDCA7L):​c.*1314G>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 0.000376 in 1,586,380 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00038 (2 hom.)
• Consequence: CDCA7L ENST00000406877.8 3_prime_UTR
• Scores: Splicing: ADA: 0.00002131
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:5
• Conservation: PhyloP100: -0.744

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 7-21901008-C-T is Benign according to our data. Variant chr7-21901008-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 257872.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Likely_benign=2, Uncertain_significance=3}. Variant chr7-21901008-C-T is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.13305C>T	p.Gly4435=	splice_region_variant, synonymous_variant	82/82	ENST00000409508.8	NP_001264044.1
CDCA7L	NM_018719.5	c.*1314G>A		3_prime_UTR_variant	10/10	ENST00000406877.8	NP_061189.2
CDCA7L	NM_001127370.3	c.*1314G>A		3_prime_UTR_variant	11/11		NP_001120842.1
CDCA7L	NM_001127371.3	c.*1314G>A		3_prime_UTR_variant	9/9		NP_001120843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.13305C>T	p.Gly4435=	splice_region_variant, synonymous_variant	82/82	5	NM_001277115.2	ENSP00000475939	P1
CDCA7L	ENST00000406877.8	c.*1314G>A		3_prime_UTR_variant	10/10	1	NM_018719.5	ENSP00000383986	P1

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152168 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000685 AC: 158 AN: 230680 Hom.: 0 AF XY: 0.000783 AC XY: 98 AN XY: 125198

Gnomad AFR exome AF: 0.000198

Gnomad AMR exome AF: 0.000366

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00250

Gnomad SAS exome AF: 0.00241

Gnomad FIN exome AF: 0.0000479

Gnomad NFE exome AF: 0.000281

Gnomad OTH exome AF: 0.00110

GnomAD4 exome AF: 0.000378 AC: 542 AN: 1434094 Hom.: 2 Cov.: 33 AF XY: 0.000436 AC XY: 310 AN XY: 710822

Gnomad4 AFR exome AF: 0.000247

Gnomad4 AMR exome AF: 0.000325

Gnomad4 ASJ exome AF: 0.0000406

Gnomad4 EAS exome AF: 0.00112

Gnomad4 SAS exome AF: 0.00278

Gnomad4 FIN exome AF: 0.0000757

Gnomad4 NFE exome AF: 0.000178

Gnomad4 OTH exome AF: 0.000677

GnomAD4 genome AF: 0.000361 AC: 55 AN: 152286 Hom.: 0 Cov.: 33 AF XY: 0.000443 AC XY: 33 AN XY: 74464

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000287 Hom.: 0

Bravo AF: 0.000321

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3 Benign:5

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:2 Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2017	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 22, 2016	- -

Primary ciliary dyskinesia Uncertain:1 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jun 03, 2015	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.73
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
dbscSNV1_RF	Benign	0.010
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: rs150682314; hg19: chr7-21940626;