rs769042639

Variant names:

• chr2-85435014-C-A
• rs769042639
• NM_001394463.1:c.590-51C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-85435014-C-A
• chr2-85435014-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001394463.1(SH2D6):​c.590-51C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000022 in 1,366,378 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.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: SH2D6 NM_001394463.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.205).

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.590-51C>A		intron	N/A	NP_001381392.1	Q7Z4S9-3
	SH2D6	NR_172131.1		n.1412-51C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2D6	ENST00000469800.7	TSL:3 MANE Select	c.590-51C>A		intron	N/A	ENSP00000510308.1	Q7Z4S9-3
	SH2D6	ENST00000340326.2	TSL:1	n.220C>A		non_coding_transcript_exon	Exon 1 of 5
	SH2D6	ENST00000389938.7	TSL:1	n.*124-51C>A		intron	N/A	ENSP00000374588.3	Q7Z4S9-4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000220 AC: 3 AN: 1366378 Hom.: 0 Cov.: 38 AF XY: 0.00000296 AC XY: 2 AN XY: 674586

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30326

American (AMR) AF: 0.00 AC: 0 AN: 30366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23822

East Asian (EAS) AF: 0.0000283 AC: 1 AN: 35332

South Asian (SAS) AF: 0.00 AC: 0 AN: 77228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3896

European-Non Finnish (NFE) AF: 0.00000188 AC: 2 AN: 1062278

Other (OTH) AF: 0.00 AC: 0 AN: 56302

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0183214), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	3.3
DANN	Benign	0.97
PhyloP100		0.17

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: rs769042639; hg19: chr2-85662137;