NM_001394463.1:c.751_753delCGCinsTGT

Variant names:

• chr2-85435684-CGC-TGT
• NM_001394463.1:c.751_753delCGCinsTGT
• SH2D6 p.Arg251Cys

Variant summary

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

The NM_001394463.1(SH2D6):​c.751_753delCGCinsTGT​(p.Arg251Cys) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R251H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SH2D6 NM_001394463.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.46
• Publications: 0 publications found

Genes affected

SH2D6 (HGNC:30439): (SH2 domain containing 6) Predicted to be involved in intracellular signal transduction and transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to be active in cytoplasm. [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_001394463.1. 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
	SH2D6	NM_001394463.1	MANE Select	c.751_753delCGCinsTGT	p.Arg251Cys	missense	N/A	NP_001381392.1	Q7Z4S9-3
	SH2D6	NR_172131.1		n.1489_1491delCGCinsTGT		non_coding_transcript_exon	Exon 19 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D6	ENST00000469800.7	TSL:3 MANE Select	c.751_753delCGCinsTGT	p.Arg251Cys	missense	N/A	ENSP00000510308.1	Q7Z4S9-3
	SH2D6	ENST00000340326.2	TSL:1	n.432_434delCGCinsTGT		non_coding_transcript_exon	Exon 3 of 5
	SH2D6	ENST00000389938.7	TSL:1	n.*201_*203delCGCinsTGT		non_coding_transcript_exon	Exon 19 of 21	ENSP00000374588.3	Q7Z4S9-4

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.5

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: chr2-85662807;