7-21900989-G-T

Variant names:

• chr7-21900989-G-T
• rs114694338
• NM_018719.5:c.*1333C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018719.5(CDCA7L):​c.*1333C>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 0.00000071 in 1,407,978 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CDCA7L NM_018719.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394
• Publications: 0 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: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, Laboratory for Molecular Medicine
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018719.5. 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
	CDCA7L	NM_018719.5	MANE Select	c.*1333C>A		3_prime_UTR	Exon 10 of 10	NP_061189.2
	DNAH11	NM_001277115.2	MANE Select	c.13304-18G>T		intron	N/A	NP_001264044.1	Q96DT5
	CDCA7L	NM_001127370.3		c.*1333C>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
	CDCA7L	ENST00000406877.8	TSL:1 MANE Select	c.*1333C>A		3_prime_UTR	Exon 10 of 10	ENSP00000383986.3	Q96GN5-1
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.13304-18G>T		intron	N/A	ENSP00000475939.1	Q96DT5
	CDCA7L	ENST00000934293.1		c.*1333C>A		3_prime_UTR	Exon 10 of 10	ENSP00000604352.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000464 AC: 1 AN: 215322 AF XY: 0.00000857

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1407978 Hom.: 0 Cov.: 33 AF XY: 0.00000144 AC XY: 1 AN XY: 695394

African (AFR) AF: 0.00 AC: 0 AN: 31456

American (AMR) AF: 0.00 AC: 0 AN: 36620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23298

East Asian (EAS) AF: 0.00 AC: 0 AN: 38918

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 76904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5516

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085348

Other (OTH) AF: 0.00 AC: 0 AN: 58052

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.44
DANN	Benign	0.71
PhyloP100		-0.39

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: rs114694338; hg19: chr7-21940607;