Genetic Variant SH2D6:c.590-69C>T (chr2-85434996-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001394463.1(SH2D6):c.590-69C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,549,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

SH2D6
NM_001394463.1 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.594

Publications

0 publications found

Variant links:

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]

SH2D6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (REVEL=0.166).

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.590-69C>T		intron	N/A	NP_001381392.1	Q7Z4S9-3
	SH2D6	NR_172131.1		n.1412-69C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SH2D6	ENST00000469800.7	TSL:3 MANE Select	c.590-69C>T	intron	N/A	ENSP00000510308.1	Q7Z4S9-3
SH2D6	ENST00000340326.2	TSL:1	n.202C>T	non_coding_transcript_exon	Exon 1 of 5
SH2D6	ENST00000389938.7	TSL:1	n.*124-69C>T	intron	N/A	ENSP00000374588.3	Q7Z4S9-4

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151768

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000311

AC:

AN:

160914

AF XY:

0.0000459

show subpopulations

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:

0.0000809

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000859

AC:

AN:

1397538

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

690444

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31864

American (AMR)

AF:

0.00

AC:

AN:

37120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24770

East Asian (EAS)

AF:

0.00

AC:

AN:

36220

South Asian (SAS)

AF:

0.00

AC:

AN:

79598

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47754

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4024

European-Non Finnish (NFE)

AF:

0.0000111

AC:

AN:

1078672

Other (OTH)

AF:

0.00

AC:

AN:

57516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151768

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74076

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41292

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

67856

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000130

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

5.5

(source)

DANN

Benign

0.78

PhyloP100

0.59

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over