chr2-209772162-C-T

Variant names:

• chr2-209772162-C-T
• rs1298596972
• NM_001371986.1:c.90C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001371986.1(UNC80):​c.90C>T​(p.Thr30Thr) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00000144 in 1,392,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UNC80 NM_001371986.1 splice_region, synonymous
• Scores: Splicing: ADA: 0.4482
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.15
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP6: Variant 2-209772162-C-T is Benign according to our data. Variant chr2-209772162-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2785677.Status of the report is criteria_provided_single_submitter, 1 stars.

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.90C>T	p.Thr30Thr	splice_region synonymous	Exon 1 of 65	NP_001358915.1	A0A669KBC5
	UNC80	NM_032504.2		c.90C>T	p.Thr30Thr	splice_region synonymous	Exon 1 of 64	NP_115893.1	Q8N2C7-1
	UNC80	NM_182587.4		c.90C>T	p.Thr30Thr	splice_region 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.90C>T	p.Thr30Thr	splice_region synonymous	Exon 1 of 65	ENSP00000501211.1	A0A669KBC5
	UNC80	ENST00000478701.1	TSL:1	n.170C>T		splice_region non_coding_transcript_exon	Exon 1 of 8
	UNC80	ENST00000439458.5	TSL:5	c.90C>T	p.Thr30Thr	splice_region synonymous	Exon 1 of 64	ENSP00000391088.1	Q8N2C7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000139 AC: 2 AN: 143872 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000821

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1392380 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 686840

African (AFR) AF: 0.00 AC: 0 AN: 30904

American (AMR) AF: 0.0000563 AC: 2 AN: 35532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24954

East Asian (EAS) AF: 0.00 AC: 0 AN: 35260

South Asian (SAS) AF: 0.00 AC: 0 AN: 79020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4500

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076318

Other (OTH) AF: 0.00 AC: 0 AN: 57586

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	-0.21
CADD	Benign	20
DANN	Benign	0.97
PhyloP100		4.2
PromoterAI		-0.14	Neutral
Mutation Taster		=42/58	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.45
dbscSNV1_RF	Benign	0.58
SpliceAI score (max)		0.010		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: rs1298596972; hg19: chr2-210636886;