16-28866155-CCC-TCG

Variant names:

• chr16-28866155-CCC-TCG
• NM_001387430.1:c.61_63delCCCinsTCG
• SH2B1 p.Pro21Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001387430.1(SH2B1):​c.61_63delCCCinsTCG​(p.Pro21Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. P21P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SH2B1 NM_001387430.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.93
• Publications: 0 publications found

Genes affected

SH2B1 (HGNC:30417): (SH2B adaptor protein 1) This gene encodes a member of the SH2-domain containing mediators family. The encoded protein mediates activation of various kinases and may function in cytokine and growth factor receptor signaling and cellular transformation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

SH2B1 Gene-Disease associations (from GenCC):

• severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387430.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2B1	NM_001387430.1	MANE Select	c.61_63delCCCinsTCG	p.Pro21Ser	missense	N/A	NP_001374359.1	Q9NRF2-1
	SH2B1	NM_001145795.2		c.61_63delCCCinsTCG	p.Pro21Ser	missense	N/A	NP_001139267.1	Q9NRF2-1
	SH2B1	NM_001308293.2		c.61_63delCCCinsTCG	p.Pro21Ser	missense	N/A	NP_001295222.1	Q9NRF2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2B1	ENST00000684370.1	MANE Select	c.61_63delCCCinsTCG	p.Pro21Ser	missense	N/A	ENSP00000507475.1	Q9NRF2-1
	SH2B1	ENST00000618521.4	TSL:1	c.61_63delCCCinsTCG	p.Pro21Ser	missense	N/A	ENSP00000481709.1	Q9NRF2-1
	SH2B1	ENST00000359285.10	TSL:1	c.61_63delCCCinsTCG	p.Pro21Ser	missense	N/A	ENSP00000352232.5	Q9NRF2-3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-28877476;