rs2069443

Variant names:

• chr7-151058086-T-A
• rs2069443
• ENST00000483786.5:c.-64+805T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-151058086-T-A
• chr7-151058086-T-G

Variant summary

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

The ENST00000483786.5(SLC4A2):​c.-64+805T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 415,672 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SLC4A2 ENST00000483786.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 0 publications found

Genes affected

SLC4A2 (HGNC:11028): (solute carrier family 4 member 2) This gene encodes a member of the anion exchanger family of membrane transport proteins. The encoded protein regulates intracellular pH, biliary bicarbonate secretion, and chloride uptake. Reduced expression of this gene may be associated with primary biliary cirrhosis (PBC) in human patients, while differential expression of this gene may be associated with malignant hepatocellular carcinoma, colon and gastric cancers. [provided by RefSeq, Nov 2016]

CDK5 (HGNC:1774): (cyclin dependent kinase 5) This gene encodes a proline-directed serine/threonine kinase that is a member of the cyclin-dependent kinase family of proteins. Unlike other members of the family, the protein encoded by this gene does not directly control cell cycle regulation. Instead the protein, which is predominantly expressed at high levels in mammalian postmitotic central nervous system neurons, functions in diverse processes such as synaptic plasticity and neuronal migration through phosphorylation of proteins required for cytoskeletal organization, endocytosis and exocytosis, and apoptosis. In humans, an allelic variant of the gene that results in undetectable levels of the protein has been associated with lethal autosomal recessive lissencephaly-7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

CDK5 Gene-Disease associations (from GenCC):

• lissencephaly 7 with cerebellar hypoplasia

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

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=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5	NM_004935.4	c.-238A>T		upstream_gene_variant		ENST00000485972.6	NP_004926.1
SLC4A2	NM_001199692.3	c.-1166T>A		upstream_gene_variant			NP_001186621.1
CDK5	NM_001164410.3	c.-238A>T		upstream_gene_variant			NP_001157882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5	ENST00000485972.6	c.-238A>T		upstream_gene_variant		1	NM_004935.4	ENSP00000419782.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000481 AC: 2 AN: 415672 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 218032

African (AFR) AF: 0.00 AC: 0 AN: 10854

American (AMR) AF: 0.00 AC: 0 AN: 13656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12936

East Asian (EAS) AF: 0.00 AC: 0 AN: 27868

South Asian (SAS) AF: 0.00 AC: 0 AN: 40434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1858

European-Non Finnish (NFE) AF: 0.00000785 AC: 2 AN: 254768

Other (OTH) AF: 0.00 AC: 0 AN: 24348

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.51
PhyloP100		0.10
PromoterAI		-0.0010	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs2069443; hg19: chr7-150755173;