rs1128226

Variant names:

• chr7-21902051-A-C
• rs1128226
• NM_018719.5:c.*271T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018719.5(CDCA7L):​c.*271T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 468,818 control chromosomes in the GnomAD database, including 28,511 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (8858 hom., cov: 34)
  • Exomes 𝑓: 0.34 (19653 hom.)
• Consequence: CDCA7L NM_018719.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 10 publications found

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]

DNAH11 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDCA7L	NM_018719.5	c.*271T>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000406877.8	NP_061189.2
CDCA7L	NM_001127370.3	c.*271T>G		3_prime_UTR_variant	Exon 11 of 11		NP_001120842.1
CDCA7L	NM_001127371.3	c.*271T>G		3_prime_UTR_variant	Exon 9 of 9		NP_001120843.1
DNAH11	NM_001277115.2	c.*797A>C		downstream_gene_variant		ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDCA7L	ENST00000406877.8	c.*271T>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_018719.5	ENSP00000383986.3
DNAH11	ENST00000409508.8	c.*797A>C		downstream_gene_variant		5	NM_001277115.2	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51181 AN: 151998 Hom.: 8861 Cov.: 34

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.335

GnomAD4 exome AF: 0.343 AC: 108606 AN: 316702 Hom.: 19653 Cov.: 3 AF XY: 0.339 AC XY: 56317 AN XY: 166012

African (AFR) AF: 0.281 AC: 2802 AN: 9962

American (AMR) AF: 0.320 AC: 4651 AN: 14532

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 4503 AN: 9856

East Asian (EAS) AF: 0.177 AC: 4070 AN: 23002

South Asian (SAS) AF: 0.266 AC: 7824 AN: 29436

European-Finnish (FIN) AF: 0.378 AC: 7097 AN: 18770

Middle Eastern (MID) AF: 0.343 AC: 474 AN: 1380

European-Non Finnish (NFE) AF: 0.369 AC: 70628 AN: 191160

Other (OTH) AF: 0.352 AC: 6557 AN: 18604

GnomAD4 genome AF: 0.336 AC: 51175 AN: 152116 Hom.: 8858 Cov.: 34 AF XY: 0.333 AC XY: 24782 AN XY: 74332

African (AFR) AF: 0.285 AC: 11846 AN: 41496

American (AMR) AF: 0.323 AC: 4940 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1620 AN: 3472

East Asian (EAS) AF: 0.181 AC: 939 AN: 5174

South Asian (SAS) AF: 0.260 AC: 1254 AN: 4822

European-Finnish (FIN) AF: 0.378 AC: 3988 AN: 10550

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25535 AN: 67994

Other (OTH) AF: 0.336 AC: 710 AN: 2112

Alfa AF: 0.360 Hom.: 15376

Bravo AF: 0.328

Asia WGS AF: 0.227 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.0
DANN	Benign	0.87
PhyloP100		-0.043
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: rs1128226; hg19: chr7-21941669; COSMIC: COSV60991159; COSMIC: COSV60991159;