rs10555456

Variant names:

• chr7-21900939-AACTT-A
• rs10555456
• NM_018719.5:c.*1379_*1382delAAGT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018719.5(CDCA7L):​c.*1379_*1382delAAGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 1,502,682 control chromosomes in the GnomAD database, including 671,147 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.86 (57323 hom., cov: 0)
  • Exomes 𝑓: 0.95 (613824 hom.)
• Consequence: CDCA7L NM_018719.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0560
• Publications: 6 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, Laboratory for Molecular Medicine
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 7-21900939-AACTT-A is Benign according to our data. Variant chr7-21900939-AACTT-A is described in ClinVar as Benign. ClinVar VariationId is 1251756.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

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.*1379_*1382delAAGT		3_prime_UTR	Exon 10 of 10	NP_061189.2
	DNAH11	NM_001277115.2	MANE Select	c.13304-63_13304-60delACTT		intron	N/A	NP_001264044.1	Q96DT5
	CDCA7L	NM_001127370.3		c.*1379_*1382delAAGT		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.*1379_*1382delAAGT		3_prime_UTR	Exon 10 of 10	ENSP00000383986.3	Q96GN5-1
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.13304-63_13304-60delACTT		intron	N/A	ENSP00000475939.1	Q96DT5
	CDCA7L	ENST00000934293.1		c.*1379_*1382delAAGT		3_prime_UTR	Exon 10 of 10	ENSP00000604352.1

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130069 AN: 151760 Hom.: 57318 Cov.: 0

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.974

Gnomad OTH AF: 0.871

GnomAD4 exome AF: 0.950 AC: 1283108 AN: 1350806 Hom.: 613824 AF XY: 0.949 AC XY: 626873 AN XY: 660316

African (AFR) AF: 0.647 AC: 19430 AN: 30026

American (AMR) AF: 0.710 AC: 20420 AN: 28766

Ashkenazi Jewish (ASJ) AF: 0.946 AC: 18720 AN: 19792

East Asian (EAS) AF: 0.714 AC: 27421 AN: 38410

South Asian (SAS) AF: 0.884 AC: 57162 AN: 64674

European-Finnish (FIN) AF: 0.978 AC: 48319 AN: 49404

Middle Eastern (MID) AF: 0.920 AC: 4822 AN: 5242

European-Non Finnish (NFE) AF: 0.978 AC: 1035160 AN: 1058772

Other (OTH) AF: 0.927 AC: 51654 AN: 55720

GnomAD4 genome AF: 0.857 AC: 130123 AN: 151876 Hom.: 57323 Cov.: 0 AF XY: 0.855 AC XY: 63433 AN XY: 74222

African (AFR) AF: 0.661 AC: 27314 AN: 41340

American (AMR) AF: 0.784 AC: 11955 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3268 AN: 3470

East Asian (EAS) AF: 0.736 AC: 3776 AN: 5132

South Asian (SAS) AF: 0.877 AC: 4218 AN: 4812

European-Finnish (FIN) AF: 0.980 AC: 10374 AN: 10582

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.974 AC: 66208 AN: 67976

Other (OTH) AF: 0.871 AC: 1837 AN: 2108

Alfa AF: 0.910 Hom.: 7792

Bravo AF: 0.829

Asia WGS AF: 0.774 AC: 2690 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.056
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: rs10555456; hg19: chr7-21940557; COSMIC: COSV60937487; COSMIC: COSV60937487;