17-7656144-G-C

Variant names:

• chr17-7656144-G-C
• rs1641512
• NM_001678.5:c.*249G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001678.5(ATP1B2):​c.*249G>C variant causes a 3 prime UTR 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: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATP1B2 NM_001678.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 14 publications found

Genes affected

ATP1B2 (HGNC:805): (ATPase Na+/K+ transporting subunit beta 2) The protein encoded by this gene belongs to the family of Na+/K+ and H+/K+ ATPases beta chain proteins, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. The glycoprotein subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes a beta 2 subunit. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

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=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP1B2	NM_001678.5	c.*249G>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000250111.9	NP_001669.3
ATP1B2	NM_001303263.2	c.*249G>C		3_prime_UTR_variant	Exon 6 of 6		NP_001290192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP1B2	ENST00000250111.9	c.*249G>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_001678.5	ENSP00000250111.4
ATP1B2	ENST00000577113.1	c.*249G>C		downstream_gene_variant		3		ENSP00000460499.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 399640 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 209422

African (AFR) AF: 0.00 AC: 0 AN: 11412

American (AMR) AF: 0.00 AC: 0 AN: 16828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12256

East Asian (EAS) AF: 0.00 AC: 0 AN: 26802

South Asian (SAS) AF: 0.00 AC: 0 AN: 41636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 240684

Other (OTH) AF: 0.00 AC: 0 AN: 22982

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.92
DANN	Benign	0.70
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1641512; hg19: chr17-7559462;