19-422284-GCG-TAA

Variant names:

• chr19-422284-GCG-TAA
• NM_012435.3:c.1480_1482delCGCinsTTA
• SHC2 p.Arg494Leu

Variant summary

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

The NM_012435.3(SHC2):​c.1480_1482delCGCinsTTA​(p.Arg494Leu) variant causes a missense change involving the alteration of a conserved nucleotide. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SHC2 NM_012435.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.33
• Publications: 0 publications found

Genes affected

SHC2 (HGNC:29869): (SHC adaptor protein 2) Predicted to enable receptor tyrosine kinase binding activity. Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to be located in cytosol. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012435.3. 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
	SHC2	NM_012435.3	MANE Select	c.1480_1482delCGCinsTTA	p.Arg494Leu	missense	N/A	NP_036567.2	P98077
	SHC2	NM_001387056.1		c.1345_1347delCGCinsTTA	p.Arg449Leu	missense	N/A	NP_001373985.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC2	ENST00000264554.11	TSL:1 MANE Select	c.1480_1482delCGCinsTTA	p.Arg494Leu	missense	N/A	ENSP00000264554.4	P98077
	SHC2	ENST00000588376.5	TSL:1	n.543_545delCGCinsTTA		non_coding_transcript_exon	Exon 1 of 3
	SHC2	ENST00000945174.1		c.1558_1560delCGCinsTTA	p.Arg520Leu	missense	N/A	ENSP00000615233.1

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		7.3

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: chr19-422284;