5-128186851-C-T

Variant names:

• chr5-128186851-C-T
• rs10089
• ENST00000509205.5:n.*472C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000509205.5(SLC12A2):​n.*472C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 401,780 control chromosomes in the GnomAD database, including 10,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3590 hom., cov: 32)
  • Exomes 𝑓: 0.23 (6804 hom.)
• Consequence: SLC12A2 ENST00000509205.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.257
• Publications: 32 publications found

Genes affected

SLC12A2 (HGNC:10911): (solute carrier family 12 member 2) The protein encoded by this gene mediates sodium and chloride transport and reabsorption. The encoded protein is a membrane protein and is important in maintaining proper ionic balance and cell volume. This protein is phosphorylated in response to DNA damage. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

SLC12A2 Gene-Disease associations (from GenCC):

• Delpire-McNeill syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal dominant 78

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Kilquist syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-128186851-C-T is Benign according to our data. Variant chr5-128186851-C-T is described in ClinVar as Benign. ClinVar VariationId is 1294739.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A2	NM_001046.3	c.*220C>T		3_prime_UTR_variant	Exon 27 of 27	ENST00000262461.7	NP_001037.1
SLC12A2	NR_046207.2	n.4114C>T		non_coding_transcript_exon_variant	Exon 27 of 27
SLC12A2	NM_001256461.2	c.*220C>T		3_prime_UTR_variant	Exon 26 of 26		NP_001243390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A2	ENST00000509205.5	n.*472C>T		non_coding_transcript_exon_variant	Exon 27 of 27	1		ENSP00000427109.1
SLC12A2	ENST00000262461.7	c.*220C>T		3_prime_UTR_variant	Exon 27 of 27	1	NM_001046.3	ENSP00000262461.2
SLC12A2	ENST00000343225.4	c.*220C>T		3_prime_UTR_variant	Exon 26 of 26	1		ENSP00000340878.4
SLC12A2	ENST00000509205.5	n.*472C>T		3_prime_UTR_variant	Exon 27 of 27	1		ENSP00000427109.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32264 AN: 151990 Hom.: 3581 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.206

GnomAD4 exome AF: 0.228 AC: 57039 AN: 249672 Hom.: 6804 Cov.: 4 AF XY: 0.227 AC XY: 29124 AN XY: 128248

African (AFR) AF: 0.183 AC: 1426 AN: 7796

American (AMR) AF: 0.322 AC: 3172 AN: 9866

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 2023 AN: 8882

East Asian (EAS) AF: 0.355 AC: 7923 AN: 22294

South Asian (SAS) AF: 0.211 AC: 1662 AN: 7874

European-Finnish (FIN) AF: 0.224 AC: 4098 AN: 18328

Middle Eastern (MID) AF: 0.176 AC: 210 AN: 1192

European-Non Finnish (NFE) AF: 0.211 AC: 33215 AN: 157578

Other (OTH) AF: 0.209 AC: 3310 AN: 15862

GnomAD4 genome AF: 0.212 AC: 32292 AN: 152108 Hom.: 3590 Cov.: 32 AF XY: 0.216 AC XY: 16030 AN XY: 74362

African (AFR) AF: 0.175 AC: 7279 AN: 41490

American (AMR) AF: 0.290 AC: 4437 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3472

East Asian (EAS) AF: 0.328 AC: 1697 AN: 5172

South Asian (SAS) AF: 0.221 AC: 1066 AN: 4820

European-Finnish (FIN) AF: 0.211 AC: 2237 AN: 10580

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14122 AN: 67976

Other (OTH) AF: 0.208 AC: 440 AN: 2112

Alfa AF: 0.212 Hom.: 11880

Bravo AF: 0.219

Asia WGS AF: 0.302 AC: 1050 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.82
CADD	Benign	6.5
DANN	Benign	0.83
PhyloP100		0.26
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: rs10089; hg19: chr5-127522543; COSMIC: COSV52478166; COSMIC: COSV52478166;