rs2297200

Variant names:

• chr20-46055887-T-A
• rs2297200
• NM_020708.5:c.2788-263T>A

Your query was ambiguous. Multiple possible variants found:

• chr20-46055887-T-A
• chr20-46055887-T-C
• chr20-46055887-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020708.5(SLC12A5):​c.2788-263T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 465,768 control chromosomes in the GnomAD database, including 27,173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8006 hom., cov: 32)
  • Exomes 𝑓: 0.34 (19167 hom.)
• Consequence: SLC12A5 NM_020708.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.463
• Publications: 6 publications found

Genes affected

SLC12A5 (HGNC:13818): (solute carrier family 12 member 5) K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 2008]

SLC12A5 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 34

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• epilepsy of infancy with migrating focal seizures

  Inheritance: AR Classification: STRONG Submitted by: G2P
• malignant migrating partial seizures of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• epilepsy, idiopathic generalized, susceptibility to, 14

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Illumina, Ambry Genetics
• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-46055887-T-A is Benign according to our data. Variant chr20-46055887-T-A is described in ClinVar as Benign. ClinVar VariationId is 1253299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A5	NM_020708.5	c.2788-263T>A		intron_variant	Intron 21 of 25	ENST00000243964.7	NP_065759.1
SLC12A5	NM_001134771.2	c.2857-263T>A		intron_variant	Intron 21 of 25		NP_001128243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A5	ENST00000243964.7	c.2788-263T>A		intron_variant	Intron 21 of 25	1	NM_020708.5	ENSP00000243964.4

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48450 AN: 151872 Hom.: 7995 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.342 AC: 107456 AN: 313776 Hom.: 19167 Cov.: 3 AF XY: 0.344 AC XY: 56967 AN XY: 165364

African (AFR) AF: 0.261 AC: 2467 AN: 9454

American (AMR) AF: 0.436 AC: 4886 AN: 11200

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 3176 AN: 9716

East Asian (EAS) AF: 0.476 AC: 9341 AN: 19624

South Asian (SAS) AF: 0.370 AC: 13509 AN: 36522

European-Finnish (FIN) AF: 0.281 AC: 5080 AN: 18090

Middle Eastern (MID) AF: 0.342 AC: 472 AN: 1382

European-Non Finnish (NFE) AF: 0.329 AC: 62488 AN: 189812

Other (OTH) AF: 0.336 AC: 6037 AN: 17976

GnomAD4 genome AF: 0.319 AC: 48477 AN: 151992 Hom.: 8006 Cov.: 32 AF XY: 0.318 AC XY: 23651 AN XY: 74298

African (AFR) AF: 0.260 AC: 10790 AN: 41430

American (AMR) AF: 0.408 AC: 6237 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1163 AN: 3468

East Asian (EAS) AF: 0.471 AC: 2433 AN: 5164

South Asian (SAS) AF: 0.371 AC: 1792 AN: 4826

European-Finnish (FIN) AF: 0.268 AC: 2838 AN: 10572

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22071 AN: 67938

Other (OTH) AF: 0.357 AC: 752 AN: 2106

Alfa AF: 0.179 Hom.: 360

Bravo AF: 0.331

Asia WGS AF: 0.462 AC: 1607 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.75
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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: rs2297200; hg19: chr20-44684526;