2-209872919-A-G

Variant names:

• chr2-209872919-A-G
• NM_001371986.1:c.3789A>G
• UNC80 p.Arg1263Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001371986.1(UNC80):​c.3789A>G​(p.Arg1263Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: UNC80 NM_001371986.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.679
• Publications: 0 publications found

Genes affected

UNC80 (HGNC:26582): (unc-80 homolog, NALCN channel complex subunit) The protein encoded by this gene is a component of a voltage-independent 'leak' ion-channel complex, in which it performs essential functions, such as serving as a bridge between two other components (sodium leak channel non-selective and UNC79) and as a scaffold for Src kinases. Leak channels play an importnat role in establishment and maintenance of resting membrane potentials in neurons. Mutations in this gene are associated with congenital infantile encephalopathy, intellectual disability and growth issues. [provided by RefSeq, Aug 2016]

UNC80 Gene-Disease associations (from GenCC):

• hypotonia, infantile, with psychomotor retardation and characteristic facies 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Illumina, Labcorp Genetics (formerly Invitae)
• hypotonia, infantile, with psychomotor retardation and characteristic facies

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=0.679 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371986.1. 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
	UNC80	NM_001371986.1	MANE Select	c.3789A>G	p.Arg1263Arg	synonymous	Exon 23 of 65	NP_001358915.1	A0A669KBC5
	UNC80	NM_032504.2		c.3795A>G	p.Arg1265Arg	synonymous	Exon 23 of 64	NP_115893.1	Q8N2C7-1
	UNC80	NM_182587.4		c.3780A>G	p.Arg1260Arg	synonymous	Exon 23 of 63	NP_872393.3	Q8N2C7-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC80	ENST00000673920.1	MANE Select	c.3789A>G	p.Arg1263Arg	synonymous	Exon 23 of 65	ENSP00000501211.1	A0A669KBC5
	UNC80	ENST00000489023.5	TSL:1	n.1320A>G		non_coding_transcript_exon	Exon 9 of 37
	UNC80	ENST00000439458.5	TSL:5	c.3795A>G	p.Arg1265Arg	synonymous	Exon 23 of 64	ENSP00000391088.1	Q8N2C7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.9
DANN	Benign	0.51
PhyloP100		0.68
Mutation Taster		=85/15	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-210737643;