2-85435077-C-A

Variant names:

• chr2-85435077-C-A
• rs752478609
• NM_001394463.1:c.602C>A

Variant summary

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

The NM_001394463.1(SH2D6):​c.602C>A​(p.Ser201*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000242 in 1,239,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: SH2D6 NM_001394463.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 2 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.602C>A	p.Ser201*	stop_gained	Exon 20 of 24	NP_001381392.1	Q7Z4S9-3
	SH2D6	NR_172131.1		n.1424C>A		non_coding_transcript_exon	Exon 18 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D6	ENST00000469800.7	TSL:3 MANE Select	c.602C>A	p.Ser201*	stop_gained	Exon 20 of 24	ENSP00000510308.1	Q7Z4S9-3
	SH2D6	ENST00000340326.2	TSL:1	n.283C>A		non_coding_transcript_exon	Exon 1 of 5
	SH2D6	ENST00000389938.7	TSL:1	n.*136C>A		non_coding_transcript_exon	Exon 18 of 21	ENSP00000374588.3	Q7Z4S9-4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000408 AC: 1 AN: 245172 AF XY: 0.00000750

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000916

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000242 AC: 3 AN: 1239398 Hom.: 0 Cov.: 37 AF XY: 0.00000489 AC XY: 3 AN XY: 614014

African (AFR) AF: 0.00 AC: 0 AN: 27020

American (AMR) AF: 0.00 AC: 0 AN: 37908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17778

East Asian (EAS) AF: 0.00 AC: 0 AN: 19530

South Asian (SAS) AF: 0.00 AC: 0 AN: 83844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3956

European-Non Finnish (NFE) AF: 0.00000206 AC: 2 AN: 968994

Other (OTH) AF: 0.0000218 AC: 1 AN: 45782

GnomAD4 genome Cov.: 30

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.0094	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	34
DANN	Benign	0.92
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.022	N
PhyloP100		-0.043
Vest4		0.029
GERP RS		-1.4
Mutation Taster		=118/82	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.31		Position offset: 46

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

Other links and lift over

dbSNP: rs752478609; hg19: chr2-85662200;