rs144467135

Variant names:

• chr3-158100317-G-A
• rs144467135
• NM_001163678.2:c.556-6C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-158100317-G-A
• chr3-158100317-G-C

Variant summary

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

The NM_001163678.2(SHOX2):​c.556-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,606 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SHOX2 NM_001163678.2 splice_region, intron
• Scores: Splicing: ADA: 0.00002412
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295
• Publications: 0 publications found

Genes affected

SHOX2 (HGNC:10854): (SHOX homeobox 2) This gene is a member of the homeobox family of genes that encode proteins containing a 60-amino acid residue motif that represents a DNA binding domain. Homeobox genes have been characterized extensively as transcriptional regulators involved in pattern formation in both invertebrate and vertebrate species. Several human genetic disorders are caused by aberrations in human homeobox genes. This locus represents a pseudoautosomal homeobox gene that is thought to be responsible for idiopathic short stature, and it is implicated in the short stature phenotype of Turner syndrome patients. This gene is considered to be a candidate gene for Cornelia de Lange syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

SHOX2 Gene-Disease associations (from GenCC):

• schizophrenia

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

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
SHOX2	NM_001163678.2	c.556-6C>T		splice_region_variant, intron_variant	Intron 2 of 4	ENST00000483851.7	NP_001157150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHOX2	ENST00000483851.7	c.556-6C>T		splice_region_variant, intron_variant	Intron 2 of 4	2	NM_001163678.2	ENSP00000419362.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000461 AC: 1 AN: 217112 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000958

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424606 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 708562

African (AFR) AF: 0.00 AC: 0 AN: 30952

American (AMR) AF: 0.00 AC: 0 AN: 32730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39302

South Asian (SAS) AF: 0.00 AC: 0 AN: 79524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5432

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1101592

Other (OTH) AF: 0.00 AC: 0 AN: 58632

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	5.5
DANN	Benign	0.39
PhyloP100		0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000024
dbscSNV1_RF	Benign	0.0
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: rs144467135; hg19: chr3-157818106;