NM_013285.3:c.2138A>C

Variant names:

• chr1-37566913-T-G
• rs1472985699
• NM_013285.3:c.2138A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013285.3(GNL2):​c.2138A>C​(p.Lys713Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: GNL2 NM_013285.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57
• Publications: 1 publications found

Genes affected

GNL2 (HGNC:29925): (G protein nucleolar 2) Enables RNA binding activity. Predicted to be involved in ribosome biogenesis. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

DNALI1 (HGNC:14353): (dynein axonemal light intermediate chain 1) This gene is the human homolog of the Chlamydomonas inner dynein arm gene, p28. The precise function of this gene is not known, however, it is a potential candidate for immotile cilia syndrome (ICS). Ultrastructural defects of the inner dynein arms are seen in patients with ICS. Immotile mutant strains of Chlamydomonas, a biflagellated algae, exhibit similar defects. [provided by RefSeq, Jul 2008]

DNALI1 Gene-Disease associations (from GenCC):

• spermatogenic failure 83

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09951022).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013285.3. 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
	GNL2	NM_013285.3	MANE Select	c.2138A>C	p.Lys713Thr	missense	Exon 16 of 16	NP_037417.1	Q5T0F3
	GNL2	NM_001323623.2		c.2342A>C	p.Lys781Thr	missense	Exon 17 of 17	NP_001310552.1
	GNL2	NM_001323624.2		c.1589A>C	p.Lys530Thr	missense	Exon 15 of 15	NP_001310553.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNL2	ENST00000373062.8	TSL:1 MANE Select	c.2138A>C	p.Lys713Thr	missense	Exon 16 of 16	ENSP00000362153.3	Q13823
	GNL2	ENST00000852774.1		c.2165A>C	p.Lys722Thr	missense	Exon 16 of 16	ENSP00000522833.1
	GNL2	ENST00000965152.1		c.2135A>C	p.Lys712Thr	missense	Exon 16 of 16	ENSP00000635211.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251456 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461814 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111942

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000579 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.079
Eigen_PC	Benign	0.020
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.6
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.16
Sift	Uncertain	0.010	D
Sift4G	Benign	0.48	T
Polyphen		0.34	B
Vest4		0.26
MVP		0.20
MPC		0.13
ClinPred		0.41	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.081
gMVP		0.075
Mutation Taster		=63/37	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: rs1472985699; hg19: chr1-38032514;