2-85436544-C-G

Variant names:

• chr2-85436544-C-G
• rs371306464
• NM_001394463.1:c.970C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001394463.1(SH2D6):​c.970C>G​(p.Arg324Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R324W) 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: -0.378
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.970C>G	p.Arg324Gly	missense	Exon 23 of 24	NP_001381392.1	Q7Z4S9-3
	SH2D6	NR_172131.1		n.1708C>G		non_coding_transcript_exon	Exon 20 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D6	ENST00000469800.7	TSL:3 MANE Select	c.970C>G	p.Arg324Gly	missense	Exon 23 of 24	ENSP00000510308.1	Q7Z4S9-3
	SH2D6	ENST00000340326.2	TSL:1	n.651C>G		non_coding_transcript_exon	Exon 4 of 5
	SH2D6	ENST00000389938.7	TSL:1	n.*420C>G		non_coding_transcript_exon	Exon 20 of 21	ENSP00000374588.3	Q7Z4S9-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	15
DANN	Uncertain	1.0
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.48	T
PhyloP100		-0.38
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Vest4		0.44
MVP		0.81
ClinPred		0.97	D
GERP RS		1.4
Mutation Taster		=68/32	polymorphism

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: rs371306464; hg19: chr2-85663667;