rs1282118966

Variant names:

• chr2-209772154-C-A
• rs1282118966
• NM_001371986.1:c.82C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-209772154-C-A
• chr2-209772154-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001371986.1(UNC80):​c.82C>A​(p.Arg28Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000129 in 1,545,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: UNC80 NM_001371986.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.24
• 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, AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Illumina
• 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=-0.19).
• BP6: Variant 2-209772154-C-A is Benign according to our data. Variant chr2-209772154-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2818403.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.24 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.82C>A	p.Arg28Arg	synonymous	Exon 1 of 65	NP_001358915.1	A0A669KBC5
	UNC80	NM_032504.2		c.82C>A	p.Arg28Arg	synonymous	Exon 1 of 64	NP_115893.1	Q8N2C7-1
	UNC80	NM_182587.4		c.82C>A	p.Arg28Arg	synonymous	Exon 1 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.82C>A	p.Arg28Arg	synonymous	Exon 1 of 65	ENSP00000501211.1	A0A669KBC5
	UNC80	ENST00000478701.1	TSL:1	n.162C>A		non_coding_transcript_exon	Exon 1 of 8
	UNC80	ENST00000439458.5	TSL:5	c.82C>A	p.Arg28Arg	synonymous	Exon 1 of 64	ENSP00000391088.1	Q8N2C7-1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151668 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1393468 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 687336

African (AFR) AF: 0.00 AC: 0 AN: 30966

American (AMR) AF: 0.00 AC: 0 AN: 35568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25010

East Asian (EAS) AF: 0.00 AC: 0 AN: 35318

South Asian (SAS) AF: 0.00 AC: 0 AN: 79030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4644

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076788

Other (OTH) AF: 0.00 AC: 0 AN: 57660

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151668 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74022

African (AFR) AF: 0.00 AC: 0 AN: 41326

American (AMR) AF: 0.00 AC: 0 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67872

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.000671 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.19
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		2.2
PromoterAI		-0.022	Neutral
Mutation Taster		=94/6	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: rs1282118966; hg19: chr2-210636878;