19-422283-G-T

Variant names:

• chr19-422283-G-T
• rs201559457
• NM_012435.3:c.1483C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_012435.3(SHC2):​c.1483C>A​(p.Arg495Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SHC2 NM_012435.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 3 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=0.098 with no splicing effect.

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.1483C>A	p.Arg495Arg	synonymous	Exon 11 of 13	NP_036567.2	P98077
	SHC2	NM_001387056.1		c.1348C>A	p.Arg450Arg	synonymous	Exon 10 of 12	NP_001373985.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHC2	ENST00000264554.11	TSL:1 MANE Select	c.1483C>A	p.Arg495Arg	synonymous	Exon 11 of 13	ENSP00000264554.4	P98077
	SHC2	ENST00000588376.5	TSL:1	n.546C>A		non_coding_transcript_exon	Exon 1 of 3
	SHC2	ENST00000945174.1		c.1561C>A	p.Arg521Arg	synonymous	Exon 12 of 14	ENSP00000615233.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.7
DANN	Benign	0.58
PhyloP100		0.098
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs201559457; hg19: chr19-422283;