7-21900988-C-T

Variant names:

• chr7-21900988-C-T
• rs141951506
• NM_018719.5:c.*1334G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. 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:3
• Conservation: PhyloP100: -2.97
• 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, Laboratory for Molecular Medicine
• 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=-0.84).
• 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 VariationId is 1574572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.*1334G>A		3_prime_UTR	Exon 10 of 10	NP_061189.2
	DNAH11	NM_001277115.2	MANE Select	c.13304-19C>T		intron	N/A	NP_001264044.1	Q96DT5
	CDCA7L	NM_001127370.3		c.*1334G>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.*1334G>A		3_prime_UTR	Exon 10 of 10	ENSP00000383986.3	Q96GN5-1
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.13304-19C>T		intron	N/A	ENSP00000475939.1	Q96DT5
	CDCA7L	ENST00000934293.1		c.*1334G>A		3_prime_UTR	Exon 10 of 10	ENSP00000604352.1

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

GnomAD2 exomes AF: 0.000576 AC: 123 AN: 213370 AF XY: 0.000537

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 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

African (AFR) AF: 0.000637 AC: 20 AN: 31378

American (AMR) AF: 0.000743 AC: 27 AN: 36334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23166

East Asian (EAS) AF: 0.000591 AC: 23 AN: 38928

South Asian (SAS) AF: 0.000824 AC: 63 AN: 76462

European-Finnish (FIN) AF: 0.000869 AC: 45 AN: 51764

Middle Eastern (MID) AF: 0.00109 AC: 6 AN: 5506

European-Non Finnish (NFE) AF: 0.000412 AC: 447 AN: 1084998

Other (OTH) AF: 0.000656 AC: 38 AN: 57956

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

African (AFR) AF: 0.000413 AC: 17 AN: 41176

American (AMR) AF: 0.00164 AC: 25 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000617 AC: 42 AN: 68020

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000688

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Primary ciliary dyskinesia (1)
-	-	1	Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.22
DANN	Benign	0.77
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism

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: rs141951506; hg19: chr7-21940606;