dbSNP rs11230562: CD6:p.Thr217Arg (chr11-61008714-C-G) – 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 ENST00000313421.11(CD6):c.650C>G(p.Thr217Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T217M) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CD6
ENST00000313421.11 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.764

Publications

0 publications found

Variant links:

Genes affected

CD6 (HGNC:1691): (CD6 molecule) This gene encodes a protein found on the outer membrane of T-lymphocytes as well as some other immune cells. The encoded protein contains three scavenger receptor cysteine-rich (SRCR) domains and a binding site for an activated leukocyte cell adhesion molecule. The gene product is important for continuation of T cell activation. This gene may be associated with susceptibility to multiple sclerosis (PMID: 19525953, 21849685). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

CD6 links:

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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 (MetaRNN=0.25487125).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000313421.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CD6	NM_006725.5	MANE Select	c.650C>G	p.Thr217Arg	missense	Exon 4 of 13	NP_006716.3
CD6	NM_001254750.2		c.650C>G	p.Thr217Arg	missense	Exon 4 of 11	NP_001241679.1
CD6	NM_001254751.2		c.650C>G	p.Thr217Arg	missense	Exon 4 of 11	NP_001241680.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CD6	ENST00000313421.11	TSL:1 MANE Select	c.650C>G	p.Thr217Arg	missense	Exon 4 of 13	ENSP00000323280.7
CD6	ENST00000352009.9	TSL:1	c.650C>G	p.Thr217Arg	missense	Exon 4 of 11	ENSP00000340628.5
CD6	ENST00000452451.6	TSL:1	c.650C>G	p.Thr217Arg	missense	Exon 4 of 11	ENSP00000390676.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454298

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722868

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

33390

American (AMR)

AF:

0.00

AC:

AN:

43950

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25972

East Asian (EAS)

AF:

0.00

AC:

AN:

39446

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85410

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51460

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108882

Other (OTH)

AF:

0.00

AC:

AN:

60032

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.022

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.31

M_CAP

Benign

0.025

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

PhyloP100

0.76

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.1

REVEL

Benign

0.092

Sift

Uncertain

0.013

Sift4G

Benign

0.062

Polyphen

0.88

Vest4

0.13

MutPred

0.59

Gain of solvent accessibility (P = 0.0058)

MVP

0.52

MPC

1.8

ClinPred

0.33

GERP RS

0.67

PromoterAI

0.055

Neutral

(source)

Varity_R

0.45

gMVP

0.77

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over